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Abstracts

Teta et al. (2008)

Teta, M.J. et al., (2008). US mesothelioma patterns 1973-2002: indicators of change and insights into background rates. European Journal of Cancer Prevention, 17: 525-534.
Abstract
Mesothelioma rates are declining toward background levels, although estimates of the background rate have varied. We expanded upon earlier analyses and provided a data-based estimate of the background rate. We analyzed US male and female patterns for five age groups using the National Cancer Institutes Surveillance Epidemiology and End Results registry data from 1973 to 2002. Age-specific and age-adjusted incidence rates per 1 000 000 persons per year, standardized to the 2000 US population, were calculated for total, pleural, and peritoneal mesothelioma. We also calculated rates for persons who attained working age after the US Occupational Safety and Health Administration asbestos exposure limits took effect. Mesothelioma rates observed among young males and females varied little over time. We observed a decline and convergence of recent male and female rates in older age groups, except those who are between the age of 60 and above, for whom the 2002 male rate was approximately five times greater than that of females. As expected, rates were higher in major shipyard areas on the West coast. Rates for persons with little or no opportunity for occupational asbestos exposure were 1.15 (95% confidence interval: 0.90-1.45) for men and 0.94 (95% confidence interval: 0.87-1.24) for women. Mesothelioma is rare in younger age groups, and rates have been relatively stable and similar for both sexes. Rates continue to decline in older age groups, but remain high for males at 60 years or older. Rates among females at older ages suggest an impact of occupational exposure. The background rate for persons below age 50 is approximately one per million, independent of sex. Future data are needed to estimate this rate for older age groups.

Antao et al. (2008)

Antao, V.C. et al. (2008). Asbestosis Mortality in the United States: Facts and Predictions. Occupational and Environmental Medicine, online 18 nov: doi:10.1136/oem.2008.039172. Abstract
Objectives: Mortality trends in the U.S. show that asbestosis deaths are increasing, while deaths related to other pneumoconiosis are declining. To analyze the association between asbestos consumption and asbestosis mortality trends. Methods: In an epidemiologic time series study, we used a modern computer intensive local regression method to evaluate the relationship between asbestos consumption per capita (1900-2006) as the predictor variable and number of asbestosis deaths (1968-2004). The predictor variable was progressively lagged by annual increments from 30 to 60 years and the goodness-of-fit assessed for each lag period. The model having the smallest Akaike's Information Criteria (AIC) was used to derive extrapolated estimates of future mortality based on more recent asbestos consumption data.
Results: Asbestos consumption per capita reached a peak in 1951 and gradually declined until 1973, when it started to drop rapidly. In 2006, it was 0.0075 kg/person/year. There were 25,564 asbestosis deaths over the period 1968-2004. The best fitting model (Adjusted R2 = 99.7%) for 1968-2004 asbestosis deaths used asbestos consumption per capita 48 years prior (1920-1956) and the log value of asbestos consumption per capita 43 years prior (1925-1961). This model predicts a total of 29,667 deaths (95% CI 19,629, 39,705) to occur during 2005-2027 (an average of 1,290 deaths per year).
Conclusions: This study demonstrates a clear association between asbestos consumption and asbestosis deaths and indicates that asbestosis deaths are not expected to decrease sharply in the next 10-15 years.

Frost et al. (2008)

Frost, G. et al. (2008). Occupational exposure to asbestos and mortality among asbestos removal workers: a Poisson regression analysis. British Journal of Cancer 99 (5): 822-29. Abstract
The asbestos industry has shifted from manufacture to stripping/removal work. The aim of this study was to investigate early indications of mortality among removal workers. The study population consisted of 31 302 stripping/removal workers in the Great Britain Asbestos Survey, followed up to December 2005. Relative risks (RR) for causes of death with elevated standardised mortality ratios (SMR) and sufficient deaths were obtained from Poisson regression. Risk factors considered included dust suppression technique, type of respirator used, hours spent stripping, smoking status and exposure length. Deaths were elevated for all causes (SMR 123, 95% CI 119-127, n=985), all cancers including lung cancer, mesothelioma, and circulatory disease. There were no significant differences between suppression techniques and respirator types. Spending more than 40 h per week stripping rather than less than 10, increased mortality risk from all causes (RR 1.4, 95% CI 1.2-1.7), circulatory disease and ischaemic heart disease. Elevated mesothelioma risks were observed for those first exposed at young ages or exposed for more than 30 years. This study is a first step in assessing long-term mortality of asbestos removal workers in relation to working practices and asbestos exposure. Further follow-up will allow the impact of recent regulations to be assessed.

Musk et al. (2008)

Musk, A.W. et al. Mortality of former crocidolite (blue asbestos) miners and millers at Wittenoom. Occup Environ Med. 2008 Aug;65(8):541-3.
Background
: Blue asbestos was mined and milled at Wittenoom in Western Australia between 1943 and 1966.
Methods: Nearly 7000 male workers who worked at the Wittenoom mine and mill have been followed up using death and cancer registries throughout Australia and Italy to the end of 2000. Person-years at risk were derived using two censoring dates in order to produce minimum and maximum estimates of asbestos effect. Standardised mortality ratios (SMRs) compare the mortality of the former Wittenoom workers with the Western Australian male population.
Results: There have been 190 cases of pleural and 32 cases of peritoneal mesothelioma in this cohort of former workers at Wittenoom. Mortality from lung cancer (SMR = 1.52), pneumoconiosis (SMR = 15.5), respiratory diseases (SMR = 1.58), tuberculosis (SMR = 3.06), digestive diseases (SMR = 1.47), alcoholism (SMR = 2.24) and symptoms, signs and ill defined conditions (SMR = 2.00) were greater in this cohort compared to the Western Australian male population. Conclusion: Asbestos related diseases, particularly malignant mesothelioma, lung cancer and pneumoconiosis, continue to be the main causes of excess mortality in the former blue asbestos miners and millers of Wittenoom

Finkelstein et al. (2008)

Finkelstein, M.M., (2008). Asbestos fibre concentrations in the lungs of brake workers: another look. Ann. Occup.Hyg. 52, 6, pp. 455-461.
Abstract
Objective:
To reanalyse data on the lung content of asbestos fibres among brake mechanics.
Methods: I re-analysed data published by Butnor, Roggli and colleagues on the lung content of chrysotile and tremolite asbestos fibres among brake mechanics and controls. Statistics of the distributions were estimated by maximum likelihood to accommodate observations below the detection limit. Mean concentrations were compared by the t-test, bootstrap resampling and interval-censored survival methods.
Results: The mean concentrations of fibres were higher among the brake workers than the controls. The concentration of tremolite fibres was higher than the concentration of chrysotile, a pattern similar to that observed among Quebec chrysotile miners and millers.
Conclusions: Re-analysis of published data does not support the interpretation that, in automotive brake repair workers with malignant mesothelioma, asbestos content is within the normal range. The alternative interpretation that brake mechanics have a greater than background burden of asbestos fibres, attributable to occupational exposure to dusts from friction products manufactured from Canadian chrysotile, appears more credible. This asbestos burden might be associated with an increased risk of asbestos-associated cancers.

Santibañez et al. (2008)

Santibañez, M. et al. (2008). Occupational exposures and risk of oesophageal cancer by histological type: a case-control study in eastern Spain. Occupational and Environmental Medicine 65(11):774-781.
Objective: To explore the relationship between occupations and specific occupational exposures and oesophageal cancer (OC) by histological type.
Methods: A multicentre hospital-based case-control study was conducted in two Mediterranean provinces of Spain. Occupational, sociodemographic and lifestyle information was collected from 185 newly diagnosed male oesophageal cancer patients (147 squamous cell, 38 adenocarcinoma) and 285 frequency matched controls. Occupation was coded according to the Spanish National Classification of Occupations 1994. Occupational exposure to a selection of carcinogenic substances was assessed by the FINJEM job exposure matrix. Odds ratios were calculated by unconditional logistic regression adjusting for age, education, alcohol intake and cigarette smoking.
Results: For the squamous cell variety, statistically significant associations were found for waiters and bartenders (OR 8.18, 95% CI 1.98 to 33.75) and miners, shotfirers, stone cutters and carvers (OR 10.78, 95% CI 1.24 to 93.7) in relation to other occupations. For the adenocarcinoma variety, statistically significant associations were observed for carpenters and joiners (OR 9.69), animal producers and related workers (OR 5.61) and building and related electricians (OR 8.26), although these observations were based on a low number of cases. Regarding specific exposures, the study found a statistically significant increased risk of squamous cell carcinoma for ionising radiation, and of adenocarcinoma for high exposure to volatile sulphur compounds (OR 3.12) and lead (OR 5.30). For all histological types of OC combined, a three-fold increase in risk was found with a significant trend for asbestos exposure (OR 3.46, 95% CI 0.99 to 12.10).
Conclusions: The data suggest that some occupational exposures may specifically increase the risk of oesophageal squamous cell carcinoma or adenocarcinoma, while other exposures such as asbestos may increase the overall risk of OC.

Pintos et al. (2008)

Pintos, J. et al. (2008). Occupational Exposure to Asbestos and Man-Made Vitreous Fibers, and Risk of Lung Cancer: Evidence From Two Case-Control Studies in Montreal, Canada. J Occup Environ Med., Nov;50(11):1273-1281.
Objective:
To examine the effects of occupational asbestos and man-made vitreous fibers (MMVF) on the risk of lung cancer in two population-based case-control studies entailing exposure at lower levels than in historic cohort studies.
Methodology: Study I (1979 to 1986) comprised 857 cases and 1066 population and cancer controls. Study II (1996 to 2001) comprised 858 cases and 1295 population controls. A detailed job history was obtained to evaluate lifetime occupational exposure to 294 agents, including asbestos and MMVF.
Results: We found increased risks for substantial exposure to asbestos (odds ratio = 1.78; 95% confidence interval: 0.94 to 3.36). The corresponding odds ratio for substantial exposure to MMVF was 1.10 (95% confidence interval: 0.37 to 3.22). Discussion: Low and moderate levels of exposure to asbestos, as encountered in this population, were associated with some excess risk of lung cancer. Results for MMVF were inconclusive.

Scnheider et al. (2008)

Schneider et al. (2008). Crocidolite and mesothelioma. Ultrastructrual Pathology, 32:171-177.
Abstract
This study reports changes in the frequency of detection of various asbestos fiber types between 1982 and 2005. Crocidolite is increasingly detected in U.S. mesothelioma patients. The percentage of crocidolite fibers detected in lung tissue has risen from 4 to 10%, and the percentage of cases in which crocidolite was detected increased from 19 to 37%. Meanwhile, the frequency of detection of amosite and chrysotile has decreased. The authors performed a detailed analysis of cases in which crocidolite was identified in the absence of amosite. Most of such cases were identified in recent years, a finding of concern since crocidolite is considered the most potent fiber type with respect to the pathogenesis of mesothelioma.

Sichletidis et al. (2008)

Sichletidis, L. et al. (2008). Mortality from Occupational Exposure to Relatively Pure Chrysotile: A 39-Year Study. Respiration. 2008 Oct 9.
Background:
Asbestos exposure is related to serious adverse health effects. However, there is disagreement about the relationship between chrysotile exposure and mesothelioma or lung cancer.
Objectives: Our aim was to investigate the mortality rate among workers exposed to relatively pure chrysotile in an asbestos cement factory.
Patients and Methods: In an asbestos cement plant opened in 1968, we prospectively studied all 317 workers. A quantity of 2,000 tons of chrysotile, with minimal amphibole contamination, was used annually until 1 January 2005. Asbestos fiber concentration was measured regularly. Date and cause of death were recorded among active and retired workers.
Results: Asbestos fiber concentration was always below permissible levels. Fifty-two workers died during the study. The cause was cancer in 28 subjects; lung cancer was diagnosed in 16 of them. No case of mesothelioma was reported. Death was attributed to cardiovascular diseases in 23 subjects and to liver cirrhosis in 1. Overall mortality rate was significantly lower than that of the Greek general population, standardized mortality ratio (SMR) was 0.71 (95% CI 0.53-0.93). Mortality due to cancer was increased (SMR 1.15, 95% CI 0.77-1.67), mainly due to lung cancer mortality (SMR 1.71, 95% CI 0.98-2.78), but not significantly.
Conclusions: Occupational exposure to relatively pure chrysotile within permissible levels was not associated with a significant increase in lung cancer or with mesothelioma. Decreased overall mortality of workers indicates a healthy worker effect, which - together with the relatively small cohort size - could have prevented small risks to be detected.

Musti et al. (2008)

Bron: Musti, M. et al. (2008). The relationship between malignant mesothelioma and an asbestos cement plant environmental risk: a spatial case-control study in the city of Bari (Italy). Int Arch Occup Environ Health. 2008 Sep 23, DOI 10.1007/s00420-00800358-5.
Abstract
Objectives:
To estimate the mesothelioma risk and environmental asbestos exposure (EAE) due to an asbestos-cement plant.
Methods: A spatial case-control study including 48 malignant mesothelioma (MM) cases occurred in the period 1993-2003 selected from the regional mesothelioma register (RMR) and 273 controls. The disease risk was estimated by means of a logistic-regression model, in which the probability of disease-occurrence is expressed as a function of the classes of distances. A non-parametric method was applied to estimate the full relative risk surface.
Results: Significant MM odds ratio of 5.29 (95 CI: 1.18-23.74) was found for people living within a range up to 500 m centered on the plant. The non-parametric estimation of relative risk surface unveiled a marked peak near the plant not paralleled by the spatial distribution of controls.
Conclusion: Evidence of an association between mesothelioma risk and EAE is highlighted. The role played by the RMR in increasing the public health local authorities awareness is stressed.

Nishikawa et al. (2008)

Nishikawa, K. et al. (2008). Recent mortality from pleural mesothelioma, historical patterns of asbestos use, and adoption of bans: a global assessment.: Environ Health Perspect. 2008 Dec;116(12):1675-80.
Abstract
Background:
In response to the health risks posed by asbestos exposure, some countries have imposed strict regulations and adopted bans, whereas other countries have intervened less and continue to use varying quantities of asbestos.
Objectives: This study was designed to assess, on a global scale, national experiences of recent mortality from pleural mesothelioma, historical trends in asbestos use, adoption of bans, and their possible interrelationships.
Methods: For 31 countries with available data, we analyzed recent pleural mesothelioma (International Classification of Diseases, 10th Revision) mortality rates (MRs) using age-adjusted period MRs (deaths/million/year) from 1996 to 2005. We calculated annual percent changes (APCs) in age-adjusted MRs to characterize trends during the period. We characterized historical patterns of asbestos use by per capita asbestos use (kilograms per capita/year) and the status of national bans.
Results: Period MRs increased with statistical significance in five countries, with marginal significance in two countries, and were equivocal in 24 countries (five countries in Northern and Western Europe recorded negative APC values). Countries adopting asbestos bans reduced use rates about twice as fast as those not adopting bans. Turning points in use preceded bans. Change in asbestos use during 1970-1985 was a significant predictor of APC in mortality for pleural mesothelioma, with an adjusted R(2) value of 0.47 (p < 0.0001).
Conclusions: The observed disparities in global mesothelioma trends likely relate to country-to-country disparities in asbestos use trends.

MacArthur et al. (2009).

MacArthur, A.C. et al. (2009). Identification of occupational cancer risk in British Columbia: A population-based case-control study of 2,998 lung cancers by histopathological subtype.American Journal of Industrial Medicine, Mar;52(3):221-232.
BACKGROUND:
Few studies have investigated occupational lung cancer risk in relation to specific histopathological subtypes. METHODS: A case-control study was conducted to evaluate the relationship between lung cancer and occupation/industry of employment by histopathological subtype. A total of 2,998 male cases and 10,223 cancer controls, diagnosed between 1983 and 1990, were identified through the British Columbia Cancer Registry. Matched on age and year of diagnosis, conditional logistic regression analyses were performed for two different estimates of exposure with adjustment for potentially important confounding variables, including tobacco smoking, alcohol consumption, marital status, educational attainment, and questionnaire respondent.
RESULTS: For all lung cancers, an excess risk was observed for workers in the primary metal (OR = 1.31, 95% CI, 1.01-1.71), mining (OR = 1.53, 95% CI, 1.20-1.96), machining (OR = 1.33, 95% CI, 1.09-1.63), transport (OR = 1.50, 95% CI, 1.08-2.07), utility (OR = 1.60, 95% CI, 1.22-2.09), and protective services (OR = 1.27, 95% CI, 1.05-1.55) industries. Associations with histopathological subtypes included an increased risk of squamous cell carcinoma in construction trades (OR = 1.25, 95% CI, 1.06-1.48), adenocarcinoma for professional workers in medicine and health (OR = 1.73, 95% CI, 1.18-2.53), small cell carcinoma in railway (OR = 1.62, 95% CI, 1.06-2.49), and truck transport industries (OR = 1.51, 95% CI, 1.00-2.28), and large cell carcinoma for employment in the primary metal industry (OR = 2.35, 95% CI, 1.11-4.96).
CONCLUSIONS: Our results point to excess lung cancer risk for occupations involving exposure to metals, polyaromatic hydrocarbons and asbestos, as well as several new histopathologic-specific associations that merit further investigation.

Rake et al. (2009)

Rake, C. et al. (2009). Occupational, domestic and environmental mesothelioma risks in the British population: a case-control study. Britsh Journal of Cancer Apr 7;100(7):1175-83.
We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8-96.8) for carpenters (LR 1 in 17), 17.1 (10.3-28.3) for plumbers, electricians and painters, 7.0 (3.2-15.2) for other construction workers, 15.3 (9.0-26.2) for other recognised high-risk occupations and 5.2 (3.1-8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (approximately 1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3-3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture.

Reid et al. (2009)

Bron: Reid A. et al. (2009). Gynecologic and breast cancers in women after exposure to blue asbestos at Wittenoom. Cancer Epidemiol Biomarkers Prev; 18(1). January 2009.
Introduction:
Animal studies have suggested an association between asbestos and ovarian cancer, and asbestos fibers have been detected in human ovaries. Sexual intercourse may introduce asbestos fibers into the vagina and to the cervix and ovaries. Occupational cohorts have reported excess mortality from reproductive cancers, but exposure-response relationships are inconsistent. We examine the incidence and exposure-response relationships of these cancers among 2,968 women and girls exposed to blue asbestos at Wittenoom, Western Australia.
Methods: 2,552 women were residents of the town and 416 worked for the asbestos company (Australian Blue Asbestos). Standardized incidence ratios compared the Wittenoom women with the Western Australian population. A nested case-control design and conditional logistic regression examined exposure-response relationships.
Results: Ovarian (standardized incidence ratio, 1.27), cervical (standardized incidence ratio, 1.44), and uterine cancer (standardized incidence ratio, 1.23) increased but not statistically significantly among the Wittenoom women compared with the Western Australian population. Among the Australian Blue Asbestos workers, cervical cancer was twice that of the Western Australian population (standardized incidence ratio, 2.38), but ovarian cancer was less (standardized incidence ratio, 0.65). Women who first arrived at Wittenoom aged >or=40 years had an odds ratio of 13.9 (95% confidence interval, 2.2-90.2) for cervical cancer compared with those aged <15 years at first arrival. Women who lived with or washed the clothes of an Australian Blue Asbestos worker did not have an increased risk for any of the gynecologic or breast cancers.
Discussion: There is no consistent evidence of an increased risk for gynecologic and breast cancers among the women from Wittenoom. Ovarian cancers and peritoneal mesotheliomas were not misclassified in this cohort.

Gordon et al. (2009)

Gordon, G.J. et al. Four-gene expression ratio test for survival in patients undergoing surgery for mesothelioma. J Natl Cancer Inst. 2009 May 6;101(9):678-86.
Background:
Malignant pleural mesothelioma has few effective treatments, one being cytoreductive surgery. We previously developed a gene ratio test to predict outcome of malignant pleural mesothelioma patients undergoing surgery. In this study, we investigated the predictive value and technical assay performance of this test in patients with malignant pleural mesothelioma.
Methods: Clinical data were obtained prospectively from 120 consecutive patients with malignant pleural mesothelioma who were scheduled for debulking surgery at one institution. Specimens were obtained at surgery or by pleural biopsy examination. Expression data for four genes were collected from tumor specimens, and three ratios of gene expression (TM4SF1/PKM2, TM4SF1/ARHGDIA, and COBLL1/ARHGDIA) were determined by quantitative reverse transcriptase-polymerase chain reaction. Patients were assigned to good or poor outcome groups by the gene ratio test. Survival was estimated by the Kaplan-Meier method and the log-rank test in univariate analyses. A multivariable Cox proportional hazards model was used to control for prognostic factors. Technical robustness was determined by using up to 30 specimens per patient, two biopsy techniques, and two performance sites. All statistical tests were two-sided.
Results: The test predicted overall survival (P < .001) and cancer-specific survival (P = .007) in univariate analysis and overall survival in multivariable analysis (hazard ratio for death = 2.09, 95% confidence interval [CI] = 1.27 to 3.45, P = .004). The test was reproducible within patients and repeatable between two determinations for specimens with widely varying tumor cell contents. Repeatability between two determinations was 88.5% (95% CI = 84.0% to 92.2%) or, when technically unacceptable test values were excluded, 91.9% (95% CI = 87.4% to 95.1%). Reproducibility between two determinations was 96.1% (95% CI = 86.5% to 99.5%). Combining the gene ratio test and other prognostic factors allowed prospective discrimination between patients at high risk (median survival = 6.9 months, 95% CI = 2.6 to 8.9 months; 3-year survival = 0%) and low risk (median survival = 31.9 months, 95% CI = 21.9 to 41.7 months; 3-year survival = 42%).
Conclusion: The gene ratio test for survival of patients with malignant pleural mesothelioma has robust predictive value and technical assay performance.

Chua, T.C. et al. (2009)

Chua, T.C. et al. (2009). Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management. Can j Surg, vol 52, Feb;52(1):59-64. 2009. Mesothelioma is an asbestos-related tumour. Mesothelioma in the thorax occurs on the pleura and is known as pleural mesothelioma. It is the more common form of mesothelioma, accounting for 70% of cases. The other form occurs in the abdomen. It accounts for much of the remaining 30% and is known as peritoneal mesothelioma. Early diagnosis of peritoneal mesothelioma is often difficult because the early symptoms are often overlooked as being a benign ailment of the gastrointestinal tract. Therefore, diagnosis often occurs at an advanced stage when disease is widespread throughout the peritoneal cavity. Treatment approaches have evolved in the last decade from systemic chemotherapy and palliative surgery to aggressive cytoreductive surgery and perioperative intraperitoneal chemotherapy. This has led to a marked increase in survival among patients who were once classified as “preterminal.” We update on the current understanding of peritoneal mesothelioma from a clinical perspective in hope that greater clinician awareness will promote best practice management of this condition

Bruin, M. de et al. (2009)

Bruin, M. de et al. (2009).Malignant mesothelioma following radiation treatment for Hodgkin’s lymphoma. Blood First Edition Paper, prepublished online February 20, 2009; DOI 10.1182/blood-2008-10-184705.
Abstract
Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the disease may be associated with radiation exposure. Recently, increased risks for second primary mesothelioma following radiation for lymphoma have been reported. Because these findings are based on small numbers of patients, they need to be confirmed. We examined mesothelioma risk in 2567 5-year survivors of Hodgkin lymphoma. The risk was almost 30-fold increased in HL patients treated with irradiation compared to the general population. Although histology and survival of the mesothelioma cases were comparable to cases from the general population, asbestos exposure and the proportion of males were lower than expected. The evidence for radiotherapy as cause for mesothelioma independent of exposure to asbestos is expanding, and the diagnosis ‘mesothelioma’ should be kept in mind whenever related symptoms arise in patients who had previous irradiation.

Loomis et al. (2009).

Loomis D, et al. (2009): Lung cancer mortality and fiber exposures among North Carolina asbestos textile workers. Occup Environ Med. 2009 Published online: Mar 11. doi:10.1136/oem.2008.044362.
Abstract
Objective:
To describe mortality among workers exposed to chrysotile asbestos and evaluate the relationship of lung cancer to asbestos fiber exposure.
Methods: Workers employed for at least 1 day between 1 January 1950 and 31 December 1973 in any of four plants in North Carolina, USA that produced asbestos textile products were enumerated. Vital status was ascertained through 31 December 2003. Historical exposures to asbestos fibers were estimated from work histories and 3578 industrial hygiene measurements taken 1935-1986. Mortality of the cohort was compared to that of the national population via standardized mortality ratios (SMRs). Exposure-response relations for lung cancer were examined within the cohort using Poisson regression to compute adjusted mortality rate ratios.
Results: Follow-up of 5770 workers included in the cohort resulted in 181,640 person-years of observation, with 2583 deaths from all causes and 277 from lung cancer. Mortality from all causes, all cancers and lung cancer was significant higher than expected, with SMRs of 1.45 for all causes, 1.34 for all cancer and 1.95 (95% CI 1.73-2.20) for lung cancer. SMRs for pleural cancer, mesothelioma and pneumoconiosis and were also elevated. The risk of lung cancer and asbestosis increased with cumulative fiber exposure (RR 1.102 per 100 fiber-year/ml, 95% CI 1.044-1.164. and RR 1.249 per 100 fiber-year/ml, 95% CI 1.186-1.316, respectively, for total career exposure). Conclusions: This study of provides further evidence that exposure to chrysotile asbestos in textile manufacturing is associated with increased risk of lung cancer, asbestosis cancer of the pleura and mesothelioma.

Mirabelli, D. et al. (2009)

Mirabelli, D. et al. (2009). Survival of peritoneal malignant mesothelioma in Italy: A population-based study. Int J Cancer. 2009 Jan 1;124(1):194-200.
Abstract
In some population-based studies, a shorter median survival was observed in peritoneal as compared with pleural, malignant mesothelioma, but in others, longer median survival times or higher proportions of long-term survivors were reported. Statistical instability could have caused these differences. We analyzed survival in peritoneal mesothelioma in a large and unselected population-based case series. Cases (338) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression) analyses of survival were performed according to selected individual characteristics, including limited treatment information in a subset of 194 cases. The results were compared with those obtained in a parallel study on pleural mesothelioma cases. Epithelioid histotype, younger age at diagnosis and, to a lesser degree, gender (women), and being diagnosed in a hospital with a thoracic surgery unit positively and significantly affected survival. The effect of treatment was positive but not statistically significant. No trend in the risk of death according to calendar period of diagnosis was present. Peritoneal mesothelioma cases had shorter median survival time than pleural cases, but a larger proportion of long-term survivors. Survival patterns after peritoneal and pleural mesothelioma differed markedly. Treatment was not associated with a statistically significant improvement in survival, but our study included cases first diagnosed before the introduction of the most recent therapeutic approaches. This provides a large historical comparison for future studies on survival trends at the population level.

Harding, A.H. et al. (2009)

Harding, A.H. et al. (2009). Mortality among British asbestos workers undergoing regular medical examinations (1971-2005). OEM Online First, published on March 1, 2009 as 10.1136/oem.2008.043414. 
Abstract
Objectives

The Great Britain Asbestos Survey was established to monitor mortality among workers covered by regulations to control occupational exposure to asbestos. This study updates the estimated burden of asbestos-related mortality in the cohort, and identifies risk factors associated with mortality.
Methods
From 1971, workers were recruited during initially voluntary and later statutory medical examinations. A brief questionnaire was completed during the medical, and participants were flagged for death registrations. Standardised Mortality Ratios (SMRs) and Proportional Mortality Ratios (PMRs) were calculated for deaths occurring before 2006. Poisson regression analyses were undertaken for diseases with significant excess mortality. Results
There were 15,496 deaths among 98,117 workers followed-up for 1,779,580 person-years. The SMR for all cause mortality was 141 (95% CI 139-143) and for all malignant neoplasms 163 (95% CI 159-167). The SMRs for cancers of the stomach (166), lung (187), peritoneum (3,730), and pleura (968), mesothelioma (513), cerebrovascular disease (164) and asbestosis (5,594) were statistically significantly elevated, as were the corresponding PMRs. In age- and sex-adjusted analysis, birth cohort, age at first exposure, year of first exposure, duration of exposure, latency, and job type were associated with the relative risk of lung, pleural, and peritoneal cancers, asbestosis and mesothelioma mortality.
Conclusions Known associations between asbestos exposure and mortality from lung, peritoneal, and pleural cancers, mesothelioma, and asbestosis were confirmed, and evidence of associations with stroke and stomach cancer mortality was observed. Limited evidence suggested that the asbestos-related disease risk may be lower among those first exposed in more recent times.

Welch, L.S. & Haile, E. (2009)

Welch, L.S. & Haile, E. (2009). Asbestos-related disease among sheet metal workers 1986-2004: radiographic changes over time. Am J Ind Med. 2009 Jul;52(7):519-25.
Background:
In 1985, the Sheet Metal Workers International Association and the Sheet Metal and Air Conditioning National Association formed The Sheet Metal Occupational Health Institute Trust (SMOHIT) to examine the health hazards of the sheet metal industry. Between 1986 and 2004 18,211 individuals were examined. At the time of the first examination 9.6% of all participants (1,745) had findings consistent with parenchymal disease (ILO > 1/0), and 21% (3,827) had pleural scarring. Methods: 2181-Two thousand hundred eighty-one who had no radiographic evidence of pneumoconiosis on baseline examination underwent a second examination.
Results: By the second examination, 5.3% had developed parenchymal disease on chest radiograph; an additional 12.4% had developed pleural scarring without parenchymal disease. Factors that predicted new cases of pneumoconiosis on radiograph were the calendar year the worker entered the sheet metal trade, smoking, and shipyard work. Forty-seven percent of those smoking at the time of initial exam reported having quit smoking by the second examination.
Conclusions: Asbestosis is still occurring 50 years after first exposure. Exposed workers benefit from medical screening programs that incorporate smoking cessation.

Cree, M.W. et al. (2009)

Cree, M.W. et al. (2009). Under-reporting of compensable mesothelioma in Alberta. Am J Ind Med. 2009 Jul;52(7):526-33. Background: When combined with a history of occupational asbestos exposure, mesothelioma is often presumed work-related. In Canada, workers diagnosed with mesothelioma caused by occupational asbestos exposure are often eligible for compensation under provincial workers' compensation boards. Although occupational asbestos exposure causes the majority of mesothelioma, Canadian research suggests less than half of workers actually apply for compensation. Alberta's mandatory reporting requirements may produce higher filing rates but this is currently unknown. This study evaluates Alberta's mesothelioma filing and compensation rates.
Methods: Demographic information on all mesothelioma patients diagnosed between 1980 and 2004 were extracted from the Alberta Cancer Board's Cancer Registry and linked to Workers' Compensation Board of Alberta claims data.
Results: Alberta recorded a total of 568 histologically confirmed mesothelioma cases between 1980 and 2004. Forty-two percent of cases filed a claim; 83% of filed claims were accepted for compensation.
Conclusions: Patient under-reporting of compensable mesothelioma is a problem and raises larger questions regarding under-reporting of other asbestos-related cancers in Alberta. Strategies should focus on increasing filing rates where appropriate.

Zucali et al. (2009)

Zucali PA, De Vincenzo F, Simonelli M, Santoro A. (2009). Future developments in the management of malignant pleural mesothelioma. Expert Rev Anticancer Ther. 2009 Apr;9(4):453-67.
Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. In the past few years, there have been several developments in the management of patients with MPM, including more accurate staging and patient selection, improvements in surgical techniques and postoperative care, novel chemotherapy regimens and new radiotherapy techniques. However, chemotherapy remains the mainstay of treatment, considering that surgery and radiotherapy have a limited role in highly selected patients, and its results are still modest, with a median survival of approximately 1 year. The principal goals of this review are to summarize the improvements in the management of MPM that have been achieved recently and to outline the therapeutic approaches in development.

McCoy et al. (2009)

McCoy MJ, Nowak AK, Lake RA. (2009). Chemoimmunotherapy: an emerging strategy for the treatment of malignant mesothelioma. Tissue Antigens. 2009 Jul;74(1):1-10.
Abstract

Whether the immune system can recognize malignant and premalignant cells and eliminate them to prevent the development of cancer is still a matter of open debate, but in our view, the balance of evidence favours this concept. Nonetheless, the International Agency for Research on Cancer has now predicted that cancer will overtake heart disease as the leading cause of death worldwide by 2010, showing that this protective mechanism often fails. Malignant mesothelioma has traditionally been considered a relatively non-immunogenic cancer. However, mesothelioma cells do express a set of well-defined tumour antigens that have been shown to engage with the host immune system. Mesothelioma should therefore be considered a target for immunotherapy. A variety of anticancer immunotherapies have been investigated in mesothelioma and in other malignancies, although these have been largely ineffective when used in isolation. Over recent years, there has been increasing interest in the possibility of combining immunotherapy with chemotherapy in the fight against cancer. Here, we discuss the rationale behind combining these two, long considered antagonistic, treatment options in the context of malignant mesothelioma.

Goodman et al. (2009)

Goodman JE, Nascarella MA, Valberg PA (2009). Ionizing radiation: a risk factor for mesothelioma. Cancer Causes Control. 2009 May 15.
Abstract
In the majority of mesothelioma cases worldwide, asbestos is a likely causal factor, but several alternative factors, such as ionizing radiation, have been recognized. We reviewed ionizing-radiation evidence from epidemiology studies of (1) patients exposed to the diagnostic X-ray contrast medium "Thorotrast," (2) patients undergoing radiation therapy (i.e., to treat cancer), and (3) atomic energy workers chronically exposed to lower levels of radiation. The results from these populations are also supported by case reports of mesothelioma following therapeutic radiation. Statistically significant associations were found in many, but not all, epidemiology studies (particularly those of Thorotrast- and radiation-treated patients). Given the low mesothelioma rate in the general population, the consistently increased risk among these radiation-exposed individuals is noteworthy. Many studies were limited by the lack of a uniform manner in which mesothelioma was reported prior to introduction of a uniform classification system (ICD-10). Future studies that rely on ICD-10 should have greater power to detect an association. While the evidence falls short of a definitive causal link, considering studies in which statistical significance was achieved, the case reports, and the plausible mode of action, we conclude that the evidence is supportive of a causal link between ionizing radiation exposure and mesothelioma risk.

Moolgavkar, S.H. et al. (2009)

Moolgavkar SH, Meza R, Turim J. (2009). Pleural and peritoneal mesotheliomas in SEER: age effects and temporal trends, 1973-2005. Cancer Causes Control, Aug;20(6):935-44.
Abstract

We analyzed mesothelioma incidence in the Surveillance, Epidemiology, and End Results (SEER) database over the period 1973-2005 using extensions of the age-period-cohort (APC) models. In these analyses, the usual non-specific age effects of the conventional APC models were replaced by hazard functions derived from two multistage models of carcinogenesis, the Armitage-Doll model and the two-stage clonal expansion (TSCE) model. The extended APC models described the incidence data on pleural and peritoneal mesotheliomas well. After adjustment for temporal trends, the data suggest that the age-specific incidence rates of both pleural and peritoneal mesotheliomas are identical in men and women. Driven largely by birth cohort effects, age-adjusted rates of pleural mesothelioma among men rose from about 7.5 per million person-years in 1973 to about 20 per million person-years in the early 1990s and appear to be stable or declining thereafter. Age-adjusted rates of pleural mesothelioma among women have remained more or less constant at about 2.5 per million person-years over the period 1973-2005. Age-adjusted rates for peritoneal mesothelioma in both men (1.2 per million person-years) and women (0.8 per million person-years) exhibit no temporal trends over the period of the study. We estimate that approximately 94,000 cases of pleural and 15,000 cases of peritoneal mesothelioma will occur in the US over the period 2005-2050.

Clin, B. et al. (2009)

Clin B, Morlais F, Dubois B, Guizard AV, Desoubeaux N, Marquignon MF, Raffaelli C, Paris C, Galateau-Salle F, Launoy G, Letourneux M. (2009). Occupational asbestos exposure and digestive cancers - a cohort study. Alimentary Pharmacology & Therapeutics, Aug 15;30(4):364-74.
Abstract
Background:
Although the role of asbestos in the genesis of mesothelioma and primary bronchopulmonary cancers has been established, results from studies focusing on the relationship between occupational exposure to asbestos and digestive cancer remain contradictory. AIM: To determine whether occupational asbestos exposure increases the incidence of digestive cancers. Methods: Our study was a retrospective morbidity study based on 2024 subjects occupationally exposed to asbestos. The incidence of digestive cancer was calculated from 1st January 1978 to 31st December 2004 and compared with levels among the local general population using Standardized Incidence Ratios. Asbestos exposure was assessed using the company's job exposure matrix
Results: Eighty-five cases of digestive cancer were observed within our cohort, for an expected number of 66.90 (SIR = 1.27 [1.01; 1.57]). A significantly elevated incidence, particularly notable among women, was observed for peritoneal mesothelioma, independently of exposure levels. A significantly elevated incidence was also noted among men for cancer of small intestine and oesophagus, for cumulative exposure indexes for asbestos above 80 fibres/mL x years. A significantly elevated incidence of cancer of the small intestine was also observed among men having been exposed to asbestos for periods in excess of 25 years and for mean exposure levels in excess of 4 fibres/mL.
Conclusions: This study suggests the existence of a relationship between exposure to asbestos and cancer of the small intestine and of the oesophagus in men.

Ray & Kindler 2009

Ray, M. & Kindler, H.L. (2009). Malignant Pleural Mesothelioma: An Update on Biomarkers and Treatment. Chest 2009; 136:888–896. Abstract
Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it was first described in South African asbestos miners. The incidence of mesothelioma parallels asbestos usage with a latency of 20 to 40 years; thus, patient numbers are declining in the United States but rising in the developing world. Radiation, genetics, and possibly simian virus 40 are less common causes. Diagnosis can be challenging, since the results of pleural fluid cytology testing are often negative despite repeated sampling. No staging system adequately predicts prognosis in the unresected patient. Newly described biomarkers, including soluble mesothelin-related peptide, megakaryocyte potentiation factor, and osteopontin, may predict which asbestos-exposed individuals will develop mesothelioma, and may prove useful in assessing response to treatment. Since surgery cannot eradicate all residual microscopic disease, a multimodality approach is encouraged. Metaanalysis suggests that pleurectomy/decortication may achieve outcomes similar to those of extrapleural penumonectomy. The standard first-line chemotherapy for unresectable disease is pemetrexed plus cisplatin. This combination improves response, survival, time to progression, pulmonary function, and disease-related symptoms. Carboplatin is often substituted, with similar results. Other active agents include raltitrexed, gemcitabine, and vinorelbine. Novel agents in clinical trials include inhibitors of the epidermal growth factor receptor, vascular endothelial growth factor, mesothelin, and histone deacetylases. Although disappointing results of early trials did not confirm promising preclinical data, recent studies have suggested that some novel agents may be effective. As we learn more about mesothelioma biology, molecularly targeted agents may become treatment options.

Dement, J.M. et al. (2009)

Dement, J.M. et al. (2009). Mortality of Older Construction and Craft Workers Employed at Department of Energy (DOE) Nuclear Sites.
Background

The U.S. Department of Energy (DOE) established medical screening programs at the Hanford Nuclear Reservation, Oak Ridge Reservation, the Savannah River Site, and the Amchitka site starting in 1996. Workers participating in these programs have been followed to determine their vital status and mortality experience through December 31, 2004.
Methods
A cohort of 8,976 former construction workers from Hanford, Savannah River, Oak Ridge, and Amchitka was followed using the National Death Index through December 31, 2004, to ascertain vital status and causes of death. Cause-specific standardized mortality ratios (SMRs) were calculated based on US death rates.
Results
Six hundred and seventy-four deaths occurred in this cohort and overall mortality was slightly less than expected (SMR¼0.93, 95% CI¼0.86–1.01), indicating a ‘‘healthy worker effect.’’ However, significantly excess mortality was observed for all cancers (SMR¼1.28, 95% CI¼1.13–1.45), lung cancer (SMR¼1.54, 95% CI¼1.24–1.87), mesothelioma (SMR¼5.93, 95% CI¼2.56–11.68), and asbestosis (SMR¼33.89, 95% CI¼18.03–57.95). Non-Hodgkin’s lymphoma was in excess at Oak Ridge and multiple myeloma was in excess at Hanford. Chronic obstructive pulmonary disease (COPD) was significantly elevated among workers at the Savannah River Site (SMR¼1.92, 95% CI¼1.02–3.29).
Conclusions DOE construction workers at these four sites were found to have significantly excess risk for combined cancer sites included in the Department of Labor’ Energy Employees Occupational Illness Compensation Program (EEOCIPA). Asbestos-related cancers were significantly elevated.

Vierikko, T. e. a. (2009)

Vierikko, T. et al. (2009). Psychological impact of computed tomography screening for lung cancer and occupational pulmonary disease among asbestos-exposed workers. European Journal of Cancer Prevention 18:203–206.
The objective of this study was to investigate the psychological impact of screening for lung cancer and occupational pulmonary disease among asbestos-exposed workers. Altogether, 633 workers were screened with chest computed tomography (627 men, 6 women, mean age 64.5 years). Participants’ views on the necessity of screening, awareness of asbestos-exposure risks, their perceived lung cancer risk, trial adherence intention, health anxiety, and worry about lung cancer were assessed. Health anxiety was reduced significantly after screening (P< 0.001). After 1 year, no significant long-term psychological differences were found between those who immediately received clear results and those who were submitted to additional examinations because of positive findings. In conclusion, computed tomography screening of pulmonary disease was well accepted and did not produce excessive long-term anxiety or other negative psychological effects, which could prevent the participation in the future screening programs.

Kumagai, S. & Kurumatani, N. (2009)

Kumagai, S. & Kurumatani, N. (2009). Asbestos fiber concentration in the area surrounding a former asbestos cement plant and excess mesothelioma deaths in residents. Am J Ind Med. 2009 Oct;52(10):790-8.
Abstract
Background:
Many persons who had lived near a former asbestos cement plant (AC plant) died from mesothelioma in Amagasaki city, Japan.
Methods: Asbestos fiber concentration in the area surrounding the AC plant was estimated so that the female mesothelioma death number predicted by a mathematical model was the same as the observed excess death number. We used the estimated asbestos fiber concentration to predict the excess mesothelioma deaths from 1970 to 2049.
Results: In a grid just south of the AC plant, the fiber concentration was estimated to be more than 3 f/ml for K(M) (asbestos potency factor for mesothelioma) of 7.75 x 10(-9). An uncertainty factor of five yields a K(M) range 1.55 x 10(-9) to 38.8 x 10(-9); these in turn correspond to fiber concentrations of 15 and 0.6 f/ml. For K(M) = 7.75 x 10(-9), grid units with higher fiber concentrations than 0.01 f/ml were estimated to extend 4.1 km (95% CI: 3.8-4.4 km) south-southwest of the plant. Over the 80-year study period (1970 to 2049), we predicted that the exposure under study will cause 346 excess mesothelioma deaths with range of 296 to 382 deaths.
Conclusions: This prediction suggests that considerable medical resources will be needed through 2049 as a result of past asbestos exposure in this region.

Goldberg, M. & Luce, D. (2009)

Goldberg, M. & Luce, D. (2009). The health impact of nonoccupational exposure to asbestos: what do we know? Eur J Cancer Prev. 2009 Jul 16.
Abstract

The objective of this study was to examine the epidemiological data that confirm the risks of pleural mesothelioma, lung cancer, and other respiratory damage associated with nonoccupational exposure to asbestos, in circumstances where exposure levels are usually lower than those found in the workplace: domestic and paraoccupational exposure to asbestos-containing material among people living with asbestos workers or near asbestos mines and manufacturing plants, environmental exposure from naturally occurring asbestos in soil, and nonoccupational exposure to asbestos-containing material in buildings. Studies concerning natural asbestos in the environment show that the exposure that begins at birth does not seem to affect the duration of the latency period, but the studies do not show whether early exposure increases susceptibility; they do not suggest that susceptibility differs according to sex. Solid evidence shows an increased risk of mesothelioma among people whose exposure comes from a paraoccupational or domestic source. The risk of mesothelioma associated with exposure as result of living near an industrial asbestos source (mines, mills, asbestos processing plants) is clearly confirmed. No solid epidemiological data currently justify any judgment about the health effects associated with passive exposure in buildings containing asbestos. Most of the studies on nonoccupational sources reported mainly amphibole exposure, but it cannot be ruled out that environmental exposure to chrysotile may also cause cancer. Nonoccupational exposure to asbestos may explain approximately 20% of the mesotheliomas in industrialized countries, but it is does not seem possible to estimate the number of lung cancers caused by these circumstances of exposure.

Druesne-Pecollo, N. e.a. (2009)

Druesne-Pecollo, N. e.a. (2009).. Beta-carotene supplementation and cancer risk: A systematic review and meta-analysis of randomized controlled trials. Int. J Cancer. 2009 Oct 28
Abstract

The effect of beta-carotene supplementation on cancer incidence has been investigated in several randomized controlled trials. The objective was to review the effect of beta-carotene supplementation on cancer incidence in randomized trials by cancer site, beta-carotene supplementation characteristics and study population. Relevant trials were retrieved by searching PubMed (up to April 2009). Authors involved in selected studies were contacted for additional information. Thirteen publications reporting results from 9 randomized controlled trials were included. Overall, no effect of beta-carotene supplementation was observed on the incidence of all cancers combined (RR, 1.01; 95% CI, 0.98-1.04), pancreatic cancer (RR, 0.99; 95% CI, 0.73-1.36), colorectal cancer (RR, 0.96; 95% CI, 0.85-1.09), prostate cancer (RR, 0.99; 95% CI, 0.91-1.07), breast cancer (RR, 0.96; 95% CI, 0.85-1.10), melanoma (RR, 0.98; 95% CI, 0.65-1.46) and non melanoma skin cancer (RR, 0.99; 95% CI, 0.93-1.05). The incidence of lung and stomach cancers were significantly increased in individuals supplemented with beta-carotene at 20-30 mg/day (RR, 1.16; 95% CI, 1.06-1.27 and RR, 1.34; 95% CI, 1.06-1.70), in smokers and asbestos workers (RR, 1.20; 95% CI, 1.07-1.34 and RR, 1.54; 95% CI, 1.08-2.19) compared to the placebo group. Beta-carotene supplementation has not been shown to have any beneficial effect on cancer prevention. Conversely, it was associated with increased risk not only of lung cancer but also of gastric cancer at doses of 20-30 mg/day, in smokers and asbestos workers. This study adds to the evidence that nutritional prevention of cancer through beta-carotene supplementation should not be recommended.

Silverstein, M.A. e.a. (2009)

Silverstein, M.A. e.a. (2009). Developments in asbestos cancer risk assessment. Am J Ind Med. 2009 Nov;52(11):850-8.
Abstract
Background:
Efforts have been made for 25 years to develop asbestos risk assessments that provide valid information about workplace and community cancer risks. Mathematical models have been applied to a group of workplace epidemiology studies to describe the relationships between exposure and risk. EPA's most recent proposed method was presented at a public meeting in July 2008.
Methods: Risk assessments prepared by USEPA, OSHA, and NIOSH since 1972 were reviewed, along with related literature. Results and Conclusions: None of the efforts to use statistical models to characterize relative cancer potencies for asbestos fiber types and sizes have been able to overcome limitations of the exposure data. Resulting uncertainties have been so great that these estimates should not be used to drive occupational and environmental health policy. The EPA has now rejected and discontinued work on its proposed methods for estimating potency factors. Future efforts will require new methods and more precise and reliable exposure assessments. However, while there may be genuine need for such work, a more pressing priority with regard to the six regulated forms of asbestos and other asbestiform fibers is to ban their production and use.

Olsson, A.C. e.a. (2009)

Olsson, A.C. e.a. (2009). Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Lung Cancer Risk: a Multicenter Study in Europe. Occup Environ Med. 2009 Sep 22.
Abstract
Background:
Lung cancer incidence in Central and Eastern Europe (CEE) is among the highest in the world, and the role of occupational exposures has not been adequately studied in these countries.
Objectives: To investigate the contribution of occupational exposure to polycyclic aromatic hydrocarbons (PAH) to lung cancer in CEE.
Methods: A case-control study was conducted in Czech Republic, Hungary, Poland, Romania, Russia, and Slovakia, as well as the United Kingdom (UK) between 1998 and 2002. Occupational and socio-demographic information was collected through interviews from 2861 newly diagnosed lung cancer cases and 2936 population or hospital controls. Industrial hygiene experts in each country evaluated exposure to 70 occupational agents, whereof 15 mixtures containing PAH. Odds ratios (OR) of lung cancer were calculated after adjusting for other occupational exposures and tobacco smoking.
Results: The OR for ever-exposure to PAH in the CEE countries was 0.93 (95% CI 0.77-1.14). The OR for the highest category of cumulative exposure, duration of exposure and intensity of exposure were 1.13 (95% CI 0.80-1.58), 1.02 (95% CI 0.66-1.57) and 1.11 (95% CI 0.60-2.05), respectively. The OR for ever PAH exposure in the UK was 1.97 (95% CI 1.16-3.35). Conclusion: Occupational PAH exposure does not appear to substantially contribute to the burden of lung cancer in CEE. The apparently stronger effect observed in the UK may be due to high exposure levels and a joint effect with asbestos.

Strand, L.A. e.a. (2009)

Strand, L.A. e.a. (2009). Asbestos-related cancers among 28,300 military servicemen in the Royal Norwegian Navy. Am J Ind Med. 2010 Jan;53(1):64-71.
Abstract
Introduction:
This study focus on the incidence of asbestos-related cancers among 28,300 officers and enlisted servicemen in the Royal Norwegian Navy. Until 1987, asbestos aboard the vessels potentially caused exposure to 11,500 crew members. Methods: Standardized incidence ratios (SIR) were calculated for malignant mesothelioma, lung cancer, and laryngeal, pharyngeal, stomach, and colorectal cancers according to service aboard between 1950 and 1987 and in other Navy personnel. Results: Increased risk of mesothelioma was seen among engine room crews, with SIRs of 6.23 (95% CI = 2.51-12.8) and 6.49 (95% CI = 2.11-15.1) for personnel who served less than 2 years and those with longer service, respectively. Lung cancer was nearly 20% higher than expected among both engine crews and non-engine crews. An excess of colorectal cancer bordering on statistical significance was seen among non-engine crews (SIR = 1.14; 95% CI = 0.98-1.32). Land-based personnel and personnel who served aboard after 1987 had lower lung cancer incidence than expected (SIR = 0.77; 95% CI = 0.64-0.92). No elevated risk of laryngeal, pharyngeal, or stomach cancers was seen.
Conclusion: The overall increase (65%) in mesotheliomas among military Navy servicemen was confined to marine engine crews only. The mesothelioma incidence can be taken as an indicator of the presence or absence of asbestos exposure, but it offered no consistent explanation to the variation in incidence of other asbestos-related cancers.

Reid, A. e.a. (2009)

Reid A, Heyworth J, de Klerk N, Musk AW (2009). Asbestos exposure and gestational trophoblastic disease: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):2895-8. Among 2,968 women and girls exposed to crocidolite (blue asbestos) at Wittenoom, three cases of choriocarcinoma and three cases of hydatidiform mole have been identified (crude incidence rate of 9.9 per 1000 women and 1.7 per 1000 deliveries for choriocarcinoma and hydatidiform mole, respectively). The women with choriocarcinoma were resident at Wittenoom at the time of disease development, whereas hydatidiform mole occurred much later in women who had first been exposed to asbestos as young girls. Four of the six cases were known to have lived with asbestos company workers who brought their dusty work-clothes home for washing. Asbestos fibers have been reported in the lung, the pleural and peritoneal mesothelium, and the human ovary. They have also been detected in placental digests of live and stillborn infants. This cluster of gestational trophoblastic diseases has some biological plausibility for asbestos causation. Taking an occupational and residential history

Pass, H.I. & Carbone, M. (2009)

Pass, H.I. & Carbone, M. (2009). Current status of screening for malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg. 2009 Summer;21(2):97-104.
Malignant mesothelioma is characterized by its association with asbestos, its long latency period, and the propensity for the diagnosis to be obtained in the later stages of the disease. Because the high-risk cohorts for mesothelioma are fairly well defined by the association with asbestos, and the exposure is usually in the workplace, it is hypothesized that early detection of the disease could (1) find patients at an earlier, more treatable stage and (2) result in prolonged survival over the present median 12 months from the start of therapy. Many studies have used standard chest X-ray to characterize changes associated with asbestos-exposed individuals, but the insensitivity of X-ray in screening patients with mesothelioma has never supported the wide-scale adaptation of such an effort. With the advent of computerized tomography, prospective trials, many of which are chiefly prevalence detection studies, have been performed and stress the importance for proper detailing by carefully qualifying suspicious changes, as well as defining the correct cohort to screen. Most recently, serum biomarkers with the potential to discriminate asbestos-exposed, non-cancer-bearing individuals from those with mesothelioma have been investigated both at single institutions and with multi-institutional-blinded trials. These markers, including soluble mesothelin-related protein, osteopontin, and megakaryocyte potentiating factor, may, in the future, be incorporated into a screening algorithm for high-risk asbestos-exposed individuals to help monitor these cohorts in a noninvasive fashion and guide the use of computerized tomography.

Aguilar-Madrid, G. e.a. (2010).

Aguilar-Madrid, G. e.a. (2010). Case-control study of pleural mesothelioma in workers with social security in Mexico. Am J Ind Med. 2010 Mar;53(3):241-51.
Background:
Environmental and occupational exposure to asbestos in Mexico in the past has been a cause of deaths and health damages. Its magnitude is unknown to date. Our objective was to identify the proportion of cases of malignant pleural mesothelioma (MPM) that can be attributed to and occupational exposure to asbestos.
Methods: We carried out a case-control study of MPM in 472 workers insured by the Mexican Institute of Social Security, all Valley of Mexico residents, with 119 incident cases and 353 controls. Cases were histologically confirmed. Participants were questioned concerning their occupational history and sociodemographic data. Assignment to one of the four exposures was performed qualitatively by an expert hygienist. Odds ratios (ORs) and attributable risks (ARs) were calculated using a non-conditional logistic regression model.
Results: A total of 80.6% of cases and 31.5% of controls had occupational exposure to asbestos. ORs were adjusted for age and gender and by exposure category, and exhibited an increase with probability of exposure as follows: 3.7(95% CI 1.3-10.4) for the likely category and 14.3(95% CI 8-26) for the certain category; AR in the group occupationally exposed to asbestos was 83.2%, and the population AR was 44%.
Conclusions: Our results show that the relationship between industrial uses of all forms of asbestos is generating an increase in mesothelioma-related diseases and deaths among Mexican workers. As a public health policy, Mexico should prohibit the use of asbestos in all production processes with the aim of controlling the epidemic and preventing the occurrence of new cases of MPM.

Rudd, R.M. (2010)

Rudd, R.M. (2010). Malignant mesothelioma. British Medical Bulletin;93:105-23.
Introduction:
Mesothelioma is a malignant tumour of the pleura or peritoneum caused by asbestos. It is increasing in frequency and the prognosis remains grim, with average survival around 1 year.
Sources of data: Medical literature and personal experience. Areas of agreement: Amphibole fibres are far more potent than chrysotile in causing mesothelioma.
Areas of controversy: A minority view suggests that mesotheliomas in those exposed to chrysotile are caused only by tremolite (an amphibole) which contaminates chrysotile. There is a hypothesis, for which evidence is weakening, that Simian virus 40 may cause mesothelioma.
Growing points: There is emerging evidence of genetic variation in susceptibility to fibre carcinogenesis. There are developments in treatment, particularly chemotherapy with pemetrexed and cisplatin which prolongs survival and helps symptoms.
Areas timely for developing research: Targeted agents for treatment are under investigation and may improve the outlook. The role of radical and palliative surgery requires clarification.

Heintz N.H. e.a. (2010)

Heintz, N.H. e.a. (2010). Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways. Am J Respir Cell Mol Biol. 2010 Feb;42(2):133-9.
Fifteen years have passed since we published findings in the AJRCMB demonstrating that induction of early response fos/jun proto-oncogenes in rodent tracheal and mesothelial cells correlates with fibrous geometry and pathogenicity of asbestos. Our study was the first to suggest that the aberrant induction of signaling responses by crocidolite asbestos and erionite, a fibrous zeolite mineral associated with the development of malignant mesotheliomas (MMs) in areas of Turkey, led to altered gene expression. New data questioned the widely held belief at that time that the carcinogenic effects of asbestos in the development of lung cancer and MM were due to genotoxic or mutagenic effects. Later studies by our group revealed that proto-oncogene expression and several of the signaling pathways activated by asbestos were redox dependent, explaining why antioxidants and antioxidant enzymes were elevated in lung and pleura after exposure to asbestos and how they alleviated many of the phenotypic and functional effects of asbestos in vitro or after inhalation. Since these original studies, our efforts have expanded to understand the interface between asbestos-induced redox-dependent signal transduction cascades, the relationship between these pathways and cell fate, and the role of asbestos and cell interactions in development of asbestos-associated diseases. Of considerable significance is the fact that the signal transduction pathways activated by asbestos are also important in survival and chemoresistance of MMs and lung cancers. An understanding of the pathogenic features of asbestos fibers and dysregulation of signaling pathways allows strategies for the prevention and therapy of asbestos-related diseases.

Ugolini, D. e.a. (2010)

Ugolini D, e.a. (2010). A bibliometric analysis of scientific production in mesothelioma research. Lung Cancer, doi:10.1016/j.lungcan.2010.01.013.
This study aims at comparing scientific production in malignant mesothelioma (MM) among countries and evaluating publication trends and impact factor (IF). The PubMed database was searched with a strategy combining keywords listed in the Medical Subject Headings and free-text search. Publications numbers and IF were evaluated both as absolute values and after standardization by population and gross domestic product (GDP). 5240 citations were retrieved from the biennium 1951-1952 (n=22) to 2005-2006 (n=535). The 177% increase of MM publications from 1987 to 2006 exceeded by large the corresponding value of total cancer literature (123.5%). In these two decades, 2559 articles with IF were published: 46.4% came from the European Union (EU) (the UK, Italy and France ranking at the top), and 36.2% from the US. The highest mean IF was reported for the US (3.346), followed by Australia (3.318), and EU (2.415, with the UK, Belgium and the Netherlands first). Finland, Sweden and Australia had the best ratio between IF (sum) and resident population or GDP. The number of publications correlated with GDP (p=0.001) and national MM mortality rates (p=0.002). An association was found between a country commitment to MM research and the burden of disease (p=0.04). Asbestos, survival, prognosis, occupational exposure, differential diagnosis, and immunohistochemistry were the most commonly used keywords. This report represents the first effort to explore the geographical and temporal distribution of MM research and its determinants. This is an essential step in understanding science priorities and developing disease control policies.

Bofetta, P. e.a. (2010)

Bofetta, P. e.a. (2010). An estimate of cancers attributable to occupational exposures in france. J Occup Environ Med. 2010 Apr;52(4):399-406.
Abstract
Objective:
To perform a quantitative estimate of the proportion of cancers attributable to occupational exposures in France in 2000.
Methods: Exposure data for established carcinogens were obtained from a 1994 survey and other sources. Relative risks for 23 exposure-cancer combinations were derived from meta-analyses and pooled analyses.
Results: A total of 4335 cases of cancer among men (2.7% of all cancers) and 403 cases among women (0.3% of all cancers) were attributed to occupational exposures. Asbestos, polycyclic aromatic hydrocarbons, and chromium VI were the main occupational carcinogens in men, and asbestos and involuntary smoking were the main carcinogens in women. Corresponding proportions for cancer deaths were 4.0% and 0.6% in men and women, respectively. Lung cancer represented 75% of deaths attributable to occupational exposures.
Conclusion: Our estimates are comparable with those obtained for other countries in studies based on similar methodology.

Fujimoto, N. e.a. (2010)

Fujimoto, N. e.a. (2010). Clinical investigation of malignant mesothelioma in Japan. J Cancer Res Clin Oncol. 2010 Mar 6. Abstract
Purpose:
The asbestos-related problems caused much social concern; however, no large-scale study was conducted about clinical features of MM in Japan. Patients with MM who have a history of occupational asbestos exposure (AE) are provided worker's compensation in Japan. However, only about 10% of MM cases were actually claimed and compensated. So there is still controversy over the association between MM and AE. The aim of this study is to investigate the clinical features of MM. We also aimed to clarify the association between MM and occupational AE in Japan.
Methods: We examined the clinical features of MM cases. Clinical information was obtained including gender, age, site of origin, pathological subtype, radiological findings, and treatment outcome. To investigate the association between MM and AE, investigators interviewed all patients regarding work and residential history.
Results: Between January 2005 and December 2007, 105 cases (median age: 63 years, range 35-80, male/female: 88/17) were diagnosed with MM in the Rosai Hospital group and related facilities. Among them, 94(89.5%) cases originated in the pleura, 7(6.7%) in the peritoneum, 2(1.9%) in the pericardium, and 1(0.9%) in the tunica vaginalis testis. There were 69(65.7%) epithelioid, 19(18.1%) biphasic, 16(15.2%) sarcomatoid, and 1 unclassified pathological subtypes of MM. A favorable survival rate was indicated in the patient group of MPM that underwent surgery compared to others, though it was not statistically significant (P = 0.1743). The occupational AE was indicated in 89 cases (84.8%). Three patients had no history of occupational AE, but lived with someone who was in an occupation that handled asbestos. There were two patients in which AE was indicated in their life environment. Altogether, AE was indicated in 93(88.6%) patients.
Conclusions: This study stresses the urgent need for physicians to acknowledge the association between MM and AE, and to inquire thoroughly regarding AE to the patients with MM.

Kishimoto, T. e.a. (2010)

Kishimoto, T. e.a. (2010). Clinical study on mesothelioma in Japan: Relevance to occupational asbestos exposure. Am J Ind Med. 2010 Jun 17.
Abstract
Background: In 2003, the number of deaths due to malignant mesothelioma in Japan was 878; however, only 85 cases of mesothelioma due to asbestos exposure were authorized for compensation. The reasons for this discrepancy require evaluation.
Method: We examined medical records, X-rays, and pathology results to evaluate mesothelioma cases in Japan between 2003 and 2005; used a questionnaire to identify occupational and environmental histories, and determined the concentration of asbestos fibers in pathology specimens.
Results: We identified 442 definite cases of malignant mesothelioma with a median age of 68 years. There were 316 malignant mesothelioma cases with occupational asbestos exposure, 12 cases with neighborhood exposure and 5 cases with likely domestic exposure. Most (78%) of the 87 cases exceeded 1,000 asbestos particles per gram of dry lung tissue. Conclusion: We conclude that 79.2% of cases of mesothelioma in Japan in recent years were caused by asbestos exposure.

Le, G.V. e.a. (2010).

Le, G.V. e.a. (2010). National use of asbestos in relation to economic development. Environ Health Perspect. 2010 Jan;118(1):116-9.
Abstract
Background:
National disparities in asbestos use will likely lead to an unequal burden of asbestos diseases. Objectives: As economic status may be linked to asbestos use, we assessed, globally, the relationship between indicators of national economic development and asbestos use.
Methods: For the 135 countries that have ever used asbestos, per capita asbestos use (kilograms per capita per year) was compared with per capita gross domestic product (GDP) in 1990 Geary-Khamis dollars (GKD) for the period 1920-2003. Countries were grouped into three income levels (high, middle, and low) that were adapted from the 2003 World Bank categories. Results: The historical pattern of asbestos use followed the environmental Kuznets curve in which use by high-income countries peaked when incomes attained 10,000-15,000 GKD and essentially ceased at income levels over 20,000 GKD. Currently, middle- and low-income countries are increasing their use of asbestos, closely following the paths once traced by higher income countries.
Conclusions: Developing countries have the opportunity to eliminate asbestos use sooner than high-income countries and thus reduce the future burden of asbestos diseases.

Klebe, S. e.a. (2010)

Klebe, S. e.a. (2010). Sarcomatoid mesothelioma: a clinical-pathologic correlation of 326 cases. Mod Pathol. 2010 Mar;23(3):470-9.
Abstract

Sarcomatoid mesothelioma is the least common, but most aggressive of the three major histological types of mesotheliomas. This study comprises 326 cases of sarcomatoid mesotheliomas among 2000 consecutive malignant mesothelioma cases received in consultation (16%). Patients included 312 men (96%) and 14 women (4%), with a median age of 70 years (range 41-94 years). Most tumors were pleural (319; 98%), and 7 were peritoneal (2%). Some desmoplastic features were identified in 110 cases (34%), and 70 (21%) were classified as desmoplastic. Rare subtypes included two cases with a lymphohistiocytoid pattern (<1%) and eight heterologous mesotheliomas (2%). Labeling for cytokeratins (CKs) was observed in 261/280 cases (93%), and for calretinin and vimentin in 31 and 91%, respectively. Pleural plaques were present in 79% of cases for which information was available, and asbestosis was diagnosed in 34/127 cases (27%). Median survival was 3.5 months. Fiber analysis was performed in 61 cases. The median asbestos body count was 1640/g wet lung tissue (by light microscopy). Amosite fibers were the most commonly identified fibers using energy-dispersive X-ray analysis and were significantly higher in the sarcomatoid cases, as were uncoated fibers using scanning electron microscopy. This study represents the largest series of sarcomatoid and desmoplastic malignant mesotheliomas to date and confirms the diagnostic usefulness of CK immunohistochemistry. The relationship with asbestos exposure--particularly amosite--and an association with pleural plaques and less often asbestosis is confirmed.

Ameille, J. e.a. (2010)

Ameille, J. e.a. (2010). Does Asbestos Exposure Cause Airway Obstruction, in the Absence of Confirmed Asbestosis? Am J Respir Crit Care Med. 2010 May 4.
Abstract
Rationale:
Whether occupational exposure to asbestos causes airway obstruction remains controversial.
Objectives: This study evaluated lung function in relation to cumulative exposure to asbestos in a large cohort of retired or unemployed asbestos-exposed workers.
Methods: The study population consisted of 3,660 volunteer subjects. An individual cumulative exposure index to asbestos was calculated for each subject, and information was obtained on smoking status. Pulmonary function tests were performed in all subjects; high resolution chest computed tomography (HRCT) was also performed in 3,335 subjects.
Measurements and main results: Values of FEV1/FVC and FEF25-75 did not differ between five classes (quintiles) of cumulative exposure to asbestos, and no significant correlation was observed between cumulative exposure to asbestos and pulmonary function parameters, after adjustment for gender, tobacco consumption, emphysema, and BMI. Furthermore, the proportion of abnormal pulmonary function tests did not differ between the five classes of cumulative exposure to asbestos. Conclusions: The results do not support a causal relationship between asbestos exposure alone and airway obstruction. However, the study sample may not be representative of all people occupationally exposed to asbestos, because a fraction of subjects with previously diagnosed asbestosis probably did not participate in this screening programme.

Larson, T.C. e.a. (2010)

Larson, T.C. e.a. (2010). Vermiculite worker mortality: estimated effects of occupational exposure to libby amphibole. J Occup Environ Med. 2010 May;52(5):555-60.
Abstract
Objective:
To examine the relationship between cumulative fiber exposure (CFE) and mortality in a retrospective cohort study of vermiculite workers exposed to Libby amphibole (n = 1862). Methods: Extended Cox regression was used to estimate the hazards associated with CFE as a time-dependent covariate of multiple-cause mortality.
Results: The Cox models for mesothelioma, asbestosis, lung cancer, and non-malignant respiratory disease were significant with rate ratios that increased monotonically with CFE. The model for deaths due to cardiovascular disease was also significant (rate ratio for CFE > or =44.0 f/cc-y vs <1.4 f/cc-y was 1.5; 95% confidence interval = 1.1 to 2.0).
Conclusions: By using a within-cohort comparison, the results demonstrate a clear exposure-response relationship between CFE and mortality from asbestos-related causes. The finding of an association between CFE and cardiovascular mortality suggests persons exposed to Libby amphibole should be monitored for this outcome.

Berman, D.W. (2010)

Berman, D.W. (2010). Comparing milled fiber, Quebec ore, and textile factory dust: Has another piece of the asbestos puzzle fallen into place? Critical Reviews in Toxicology, 2010; 40(2): 151–188.
Abstract

Results of a meta-analysis indicate that the variation in potency factors observed across published epidemiology studies can be substantially reconciled (especially for mesothelioma) by considering the effects of fiber size and mineral type, but that better characterization of historical exposures is needed before improved exposure metrics potentially capable of fully reconciling the disparate potency factors can be evaluated. Therefore, an approach for better characterizing historical exposures, the Modified Elutriator Method (MEM), was evaluated to determine the degree that dusts elutriated using this method adequately mimic dusts generated by processing in a factory. To evaluate this approach, elutriated dusts from Grade 3 milled fiber (the predominant feedstock used at a South Carolina [SC] textile factory) were compared to factory dust collected at the same facility. Elutriated dusts from chrysotile ore were also compared to dusts collected in Quebec mines and mills. Results indicate that despite the substantial variation within each sample set, elutriated dusts from Grade 3 fiber compare favorably to textile dusts and elutriated ore dusts compare to dusts from mines and mills. Given this performance, the MEM was also applied to address the disparity in lung cancer mortality per unit of exposure observed, respectively, among chrysotile miners/millers in Quebec and SC textile workers. Thus, dusts generated by elutriation of stockpiled chrysotile ore (representing mine exposures) and Grade 3 milled fiber (representing textile exposures) were compared. Results indicate that dusts from each sample differ from one another. Despite such variation, however, the dusts are distinct and fibers in Grade 3 dusts are significantly longer than fibers in ore dusts. Moreover, phase-contrast microscopy (PCM) structures in Grade 3 dusts are 100% asbestos and counts of PCM-sized structures are identical, whether viewed by PCM or transmission electron microscope (TEM). In contrast, a third of PCM structures in ore dusts are not asbestos and only a third that are counted by PCM are also counted by TEM. These distinctions also mirror the characteristics of the bulk materials themselves. Perhaps most important, when the differences in size distributions and PCM/TEM distinctions in these dusts are combined, the combined difference is sufficient to completely explain the difference in exposure/response observed between the textile worker and miner/miller cohorts. Importantly, however, evidence that such an explanation is valid can only be derived from a meta-analysis (risk assessment) covering a diverse range of epidemiology study environments, which is beyond the scope of the current study. The above findings suggest that elutriator-generated dusts mimic factory dusts with sufficient reliability to support comparisons between historical exposures experienced by the various cohorts studied by epidemiologists. A simulation was also conducted to evaluate the relative degree that the characteristics of dust are driven by the properties of the bulk material processed versus the nature of the mechanical forces applied. That results indicate it is the properties of bulk materials reinforces the theoretical basis justifying use of the elutriator to reconstruct historical exposures. Thus, the elutriator may be a valuable tool for reconstructing historical exposures suitable for supporting continued refinements of the risk models being developed to predict asbestos-related cancer risk.

Kao, S.C. e.a. (2010)

Kao, S.C. e.a. (2010) Malignant Mesothelioma. Internal Medicine Journal, Mar 18.
Abstract

Malignant mesothelioma (MM) is an aggressive tumour that commonly affects the mesothelial surfaces of the pleural and peritoneal cavities, and occasionally, the tunica vaginalis and the pericardium. Formerly a rare tumour, MM is increasing in incidence in Australia due to the heavy nationwide use of asbestos from 1940 until the 1980s. The incidence is expected to peak in Australia in the next decade, mirroring the long latency period between asbestos exposure and development of MM. Diagnosis of MM can be difficult. Definitive pathological diagnosis is required and it often requires an experienced pathologist to differentiate MM from other benign or malignant processes. Treatment of MM requires a multidisciplinary approach, regardless of palliative or curative intent. Treatment options such as surgery, chemotherapy, radiotherapy and active symptom control or a combination of these may be employed. Further research is needed to advance the therapeutic options for MM, and strategies to realise personalisation of therapy through discovery of predictive markers. In the Australian society where asbestos contamination of the built environment is very high, education and stringent public health measures are required to prevent a second wave of increased MM incidence.

Goldberg, S. e.a. (2010)

Goldberg, S. e.a. (2010). Possible effect of environmental exposure to asbestos on geographical variation in mesothelioma rates. Occup Enivon Med 2010 67: 417-421.
Abstract
Background:
In population-based mesothelioma studies in industrialised countries, the incidence of mesothelioma without any identified asbestos exposure (IAE) is usually higher among women, while male incidence is mainly attributed to IAE. Through a comparison of the spatial distribution of male and female rates, and IAE and no IAE incidence, this study investigated whether mesotheliomas without IAE are in fact induced by non-recognised asbestos exposure, mostly from environmental sources.
Methods: We calculated mesothelioma mortality (SMR) and incidence (SIR) ratios by district in France, pooling 30 and 10 years of data, respectively. Using correlation coefficients, we compared geographical patterns of male and female mesothelioma ratios, and IAE and no IAE mesothelioma ratios. Results: The raw numbers of male and female mesothelioma cases were equivalent. Mesothelioma SMR (0.76) and SIR (0.80) geographical correlations between men and women were strongly positive. SIR correlation between occupationally IAE and no IAE cases was also positive (0.69). Correlation between occupationally IAE and no IAE cases was positive among women but not among men.
Conclusions: Data analyses of mesothelioma mortality and incidence showed that female cases occur in the same geographical areas as male cases. Female mesotheliomas with no IAE occur in the same geographical areas as exposed cases, suggesting asbestos has a major influence on female mesothelioma, likely through environmental exposure

Antonescu-Turcu, A.L. & Schapira, R.M. (2010)

Antonescu-Turcu, A.L. & Schapira, R.M. (2010). Parenchymal and airway diseases caused by asbestos. Curr Opin Pulm Med. 2010 Mar;16(2):155-61.
Abstract
Purpose of Review:
The extensive industrial use of asbestos for many decades has been linked to development of benign and malignant pleuropulmonary disease. This review summarizes newer evidence and ongoing controversies that exist in the literature regarding asbestos-related parenchymal and airway diseases.
Recent findings: Asbestosis represents a significant respiratory problem despite the improvement in the workplace hygiene and a decrease in use of asbestos. The management of asbestosis remains challenging as currently there is no specific treatment. The role of asbestos exposure alone as a cause of chronic airway obstruction remains uncertain. The relationship between lung cancer and asbestos exposure alone and in combination with smoking has also been investigated. The benefit of screening for asbestos-related pleuropulmonary disease remains uncertain as does the use of computed tomography scanning for the purpose of screening.
Summary: Future studies will help clarify the clinical issues and shape screening strategies for asbestos-exposed individuals.

Price, B. (2010)

Price, B. (2010). Industrial-grade talc exposure and the risk of mesothelioma. Crit Rev Toxicol. 2010.Jul;40(6):513-30. Abstract
Industrial-grade talc deposits are complex mixtures of mineral particles and may vary substantially in composition across small geographical areas. Typical industrial-grade talc includes amphibole cleavage fragments, platy talc, serpentine minerals, talc in fibrous form, and a minor presence of transitional fibers. Industrial-grade talc was erroneously determined to be an asbestos-containing material due to an unintended consequence of Occupational Health and Safety Administration's (OSHA's) method for measuring airborne asbestos mandated in 1972. This error was repeated, most notably, by the National Institute for Occupational Safety and Health (NIOSH) in, 1980 for talc mined in northern New York State (NYS) by RT Vanderbilt Company (RTV). Subsequent exposure studies of northern NYS talc conducted through the, 1980s and one study published after, 2000 relied on the conclusion that talc was an asbestos-containing material to infer a causal relationship between talc and mesothelioma. The present review included (1) publications concerning talc's cancer-causing potential issued by organizations concerned with occupational and public health; (2) talc exposure studies and animal and cellular studies of RTV talc; (3) mesothelioma rates in northern NYS; and (4) mesothelioma mortality among RTV mining employees. The review indicated that failure to correctly identify the mineral characteristics of talc resulted in misleading reports concerning the carcinogenic potential of talc. However, the collective data from animal and cellular studies, mesothelioma rates in northern NYS, exposure studies, and a mortality analysis of RTV mining employees do not support a causal relationship between RTV talc and mesothelioma. This conclusion is applicable to all mineral components in RTV talc and to other industrial-grade talcs and mineral aggregates with the same components.

Pacurari, M. e.a. (2010)

Pacurari, M. e.a. (2010). Single- and multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes a new health risk to humans? J Toxicol Environ Health 2010 Jan;73(5):378-95.
Abstract

Carbon nanotubes (CNT), since their discovery, have become one of the most promising nanomaterials in many industrial and biomedical applications. Due to their unique physicochemical properties, interest is growing in the manufacture of CNT-based products and their subsequent marketing. Since their discovery, the prospect of possible undesirable human health effects has been a focus of many scientific studies. Although CNT possess unique physical properties that include (1) nanoscale diameter, (2) a wide length distribution ranging from tens of nanometers to several micrometers, and (3) high aspect ratio, the fibrous-like shape and durability suggest that their toxic properties may be analogous to those observed with other fibrous particles, such as asbestos. The present study provides a summary of published findings on CNT bioactivity, such as the potential of CNT, especially of multi-wall carbon nanotubes (MWCNT), to activate signaling pathways modulating transcription factor activity, induce apoptosis, induce DNA damage, and initiate biological responses. Assessment of risks to human health and adoption of appropriate exposure controls is critical for the safe and successful introduction of CNT -based products for future applications.

Donaldson, K. e.a. (2010)

Donaldson, K. e.a. (2010). Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol. 2010 Mar 22;7:5.
Abstract

The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura. othelioma.

Vudrag, M. e.a. (2010)

Vudrag, M. e.a. (2010). Mesothelioma risk associated with asbestos production in slovenia. Arh Hig Rada Toksikol. 2010 Mar;61(1):45-52.
Abstract
The aim of this study was to assess malignant mesothelioma morbidity due to exposure to asbestos in a population living in districts Nova Gorica and Tolmin (49,850 people) near the asbestos manufacturing village Anhovo (Slovenia) and to compare it with the entire Slovene population (1,949,750 people). Crude rates per 100,000 people were calculated from the total number of mesotheliomas, and risk assessment in the studied vs. total population was based on 23 years worth of data. Time series data on mesothelioma cases were also processed as a forecast of new cases by 2010.The crude incidence of mesothelioma per 100,000 individuals for all of Slovenia was 21.4, while for the Nova Gorica district including the village Anhovo it is 170.2 and for the Tolmin district 60.9. The probability of a mesothelioma case in the studied population was 8.5 times the probability of the same diagnosis in the whole of Slovenia. Over 23 years, 28% of all mesothelioma cases in Slovenia were diagnosed in the studied population, which makes only 2.5% of the total Slovene population.The outbreak of asbestosis and mesothelioma epidemics in the studied population is associated with manufacture of asbestos products in the local factory from 1922 to 1996.

Abejie, B.A. e.a. (2010).

Abejie, B.A. e.a. (2010). Patterns of pulmonary dysfunction in asbestos workers: a cross-sectional study. J Occup Med Toxicol. 2010; 5: 12. Online op 3 juni 2010, doi: 10.1186/1745-6673-5-12.
Abstract
Background:
Restrictive patterns of pulmonary function abnormalities associated with asbestos exposure are well described. Studies are less consistent, however, regarding the association of asbestos inhalation with airway dysfunction and obstructive impairment.
Methods: We compared pulmonary function test results between 277 chrysotile exposed workers (22% non-smokers) and 177 unexposed controls (50.3% non-smokers). Information on exposure and smoking were collected using a standardized questionnaire. Standardized spirometric and DCLO Measurement methods were utilized. CXRs were read based on ILO pneumoconiosis guidelines.
Results: Asbestos exposed subjects had significantly reduced FVC, FEV1, FEV1/FVC and DLCO. Restricting the analysis to non-smokers, asbestos workers still had about 3% lower FEV1/FVC ratio than controls, but this difference did not reach statistical significance. Among exposed workers, the presence of radiographic evidence of asbestosis further lowered FVC and DLCO but not FEV1/FVC compared to asbestos exposure without radiographic asbestosis. Additionally, smoking asbestos workers had significantly lower DLCO compared to non-smoking workers. Conclusion: Asbestos exposure, especially when radiographic evidence of interstitial fibrosis from asbestosis is present, leads to significant decreases in FVC, FEV1 and the DLCO. However, asbestos exposure alone is not significantly associated with a reduction of the FEV1/FVC. Smoking-asbestos workers had significantly lower DLCO than their non-smoking counterparts. Whether asbestos interacts with smoking additively or synergistically on DLCO needs further investigation. Similarly, further studies are needed to assess the progression and clinical significance of asbestos induced airway dysfunction.

Ladou, J. e.a. (2010).

Ladou, J. e.a. (2010). The case for a global ban on asbestos. Environ Health Perspect. 2010 Jul;118(7):897-901.
Abstract
Background:
All forms of asbestos are now banned in 52 countries. Safer products have replaced many materials that once were made with it. Nonetheless, many countries still use, import, and export asbestos and asbestos-containing products, and in those that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos is often exempted from the ban. In fact, chrysotile has accounted for > 95% of all the asbestos used globally.
Objective: We examined and evaluated the literature used to support the exemption of chrysotile asbestos from the ban and how its exemption reflects the political and economic influence of the asbestos mining and manufacturing industry.
Discussion: All forms of asbestos, including chrysotile, are proven human carcinogens. All forms cause malignant mesothelioma and lung and laryngeal cancers, and may cause ovarian, gastrointestinal, and other cancers. No exposure to asbestos is without risk. Illnesses and deaths from asbestos exposure are entirely preventable. .

Collegium Ramazzini (2010)

Collegium Ramazzini (2010). Commentary : Asbestos Is Still with Us : repeat Call for a Universal Ban. International journal of occupational and environmental health, vol. 23 (2) : 201-207. Abstract
All forms of asbestos are proven human carcinogens. All forms of asbestos cause malignant mesothelioma, lung, and laryngeal cancers, and may cause ovarian, gastrointestinal and other cancers. No exposure to asbestos is without risk, and there is no safe threshold of exposure to asbestos. Asbestos cancer victims die painful lingering deaths. These deaths are almost entirely preventable. When evidence of the carcinogenicity of asbestos became incontrovertible, the concerned parties, including the Collegium Ramazzini, called for a universal ban on the mining, manufacture and use of asbestos in all countries around the world [1]. Asbestos is now banned in 52 countries [2], and safer products have replaced many materials that once were made with asbestos. Nonetheless, a large number of countries still use, import, and export asbestos and asbestos-containing products. And in many countries that have banned other forms of asbestos, the so-called “controlled use” of chrysotile asbestos continues to be permitted, an exemption that has no basis in medical science but rather reflects the political and economic influence of the asbestos mining and manufacturing industry. To protect the health of all people in the world — industrial workers, construction workers, women and children, now and in future generations — the Collegium Ramazzini calls again today on all countries of the world, as we have repeatedly in the past, to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed.

Tan, E., e.a. (2010)

Tan, E. e.a. (2010). Projection of mesothelioma mortality in Britain using Bayesian methods. Br J Cancer. 2010 Jul 27;103(3):430-6.
Abstract
Background:
Mesothelioma mortality has increased more than ten-fold over the past 40 years in Great Britain, with >1700 male deaths recorded in the British mesothelioma register in 2006. Annual mesothelioma deaths now account for >1% of all cancer deaths. A Poisson regression model based on a previous work by Hodgson et al has been fitted, which has allowed informed statistical inferences about model parameters and predictions of future mesothelioma mortality to be made.
Methods: In the Poisson regression model, the mesothelioma risk of an individual depends on the average collective asbestos dose for the individual in a given year and an age-specific exposure potential. The model has been fitted to the data within a Bayesian framework using the Metropolis-Hastings algorithm, a Markov Chain Monte Carlo technique, providing credible intervals for model parameters as well as prediction intervals for the number of future cases of mortality.
Results: Males were most likely to have been exposed to asbestos between the ages of 30 and 49 years, with the peak year of asbestos exposure estimated to be 1963. The estimated number of background cases was 1.08 cases per million population.
Conclusion: Mortality among males is predicted to peak at approximately 2040 deaths in the year 2016, with a rapid decline thereafter. Approximately 91,000 deaths are predicted to occur from 1968 to 2050 with around 61,000 of these occurring from 2007 onwards.

Alfonso H.S. e.a. (2010)

Alfonso H.S. e.a. (2010). Retinol supplementation and mesothelioma incidence in workers earlier exposed to blue asbestos (Crocidolite) at Wittenoom, Western Australia. Eur J Cancer Prev. 2010 Sep;19(5):355-9.
Abstract
Owing to the high rates of malignant mesothelioma in workers exposed to crocidolite earlier at Wittenoom and evidence of protection against cancer by vitamin A, a population-based cancer prevention programme providing retinol supplements (25 000 IU/day) was commenced in 1990. The former workers at Wittenoom known to be alive and living in Western Australia in June 1990 constitute the study population. The participants were classified into two groups: those who received supplemental retinol (intervention group) and those who received none (comparison group). The relative rate of mesothelioma for those receiving retinol was estimated using Cox regression, adjusting for cumulative asbestos exposure and age at first exposure to asbestos. Nine hundred and twenty-eight former Wittenoom workers received retinol at some stage of the programme, whereas 1471 workers never received retinol (comparison group). Those who received retinol were younger, had a greater exposure to asbestos and smoked less than the comparison group. There were 65 cases of mesothelioma in the retinol group and 88 in the comparison group. After adjustment, the hazard ratio was 0.99 (95% confidence interval=0.70-1.41). This result did not alter when the participants who received only retinol once or those who received beta-carotene earlier were excluded from the analysis. In conclusion, this study provides little support for possible preventive effects of retinol against mesothelioma in workers exposed to blue asbestos.

Yang, H. e.a. (2010)

Yang, H. e.a. (2010). Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12611-6.
Abstract
Asbestos carcinogenesis has been linked to the release of cytokines and mutagenic reactive oxygen species (ROS) from inflammatory cells. Asbestos is cytotoxic to human mesothelial cells (HM), which appears counterintuitive for a carcinogen. We show that asbestos-induced HM cell death is a regulated form of necrosis that links to carcinogenesis. Asbestos-exposed HM activate poly(ADP-ribose) polymerase, secrete H(2)O(2), deplete ATP, and translocate high-mobility group box 1 protein (HMGB1) from the nucleus to the cytoplasm, and into the extracellular space. The release of HMGB1 induces macrophages to secrete TNF-alpha, which protects HM from asbestos-induced cell death and triggers a chronic inflammatory response; both favor HM transformation. In both mice and hamsters injected with asbestos, HMGB1 was specifically detected in the nuclei, cytoplasm, and extracellular space of mesothelial and inflammatory cells around asbestos deposits. TNF-alpha was coexpressed in the same areas. HMGB1 levels in asbestos-exposed individuals were significantly higher than in nonexposed controls (P < 0.0001). Our findings identify the release of HMGB1 as a critical initial step in the pathogenesis of asbestos-related disease, and provide mechanistic links between asbestos-induced cell death, chronic inflammation, and carcinogenesis. Chemopreventive approaches aimed at inhibiting the chronic inflammatory response, and especially blocking HMGB1, may decrease the risk of malignant mesothelioma among asbestos-exposed cohorts.

Pasello, G. & Favoretto, A. (2009).

Pasello, G. & Favoretto, A. (2010). Molecular targets in malignant pleural mesothelioma treatment. Curr Drug Targets. 2009 Dec;10(12):1235-44. 
Abstract

Malignant mesothelioma is an aggressive tumour of the serosal surfaces with poor prognosis and increasing incidence due to widespread previous asbestos exposure. Relative chemotherapeutic and radiotherapeutic resistance makes malignant pleural mesothelioma (MPM) difficult to manage, even though encouraging results were achieved with multimodality treatment. Better knowledge of angiogenesis and molecular pathways involved in MPM seems to be the right way to define new targets for systemic treatment. Neoangiogenesis may be considered as a critical step in the development of mesothelioma. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are autocrine growth factors in MPM and epidermal growth factor receptor (EGFR) appears highly expressed in this tumour. Tyrosine kinase inhibitors (TKIs) targeting growth factors like vandetanib, dasatinib, and angiogenesis inhibitors like bevacizumab, are among the most promising agents under evaluation in clinical trials. Mesothelioma is a malignancy which owes its chemoresistance to an apoptotic defect. Thus the introduction of new biologic drugs like vorinostat, bortezomib, everolimus and temsirolimus, in the treatment of MPM finds a strong rationale. This review focuses on the current target therapies and evaluates future biologic approaches for the systemic management of MPM.

Finkelstein, M.M. (2010)

Finkelstein, M.M. (2010). Absence of radiographic asbestosis and the risk of lung cancer among asbestos-cement workers: Extended follow-up of a cohort. Am J Ind Med. 2010 Jul 29. Abstract
Background:
It has been a matter of controversy whether there is an increased risk of lung cancer among asbestos-exposed workers without radiographic asbestosis. A previous study of lung cancer risk among asbestos-cement workers has been updated with an additional 12 years of follow-up.
Methods: Subjects had received radiographic examination at 20 and 25 years from first exposure to asbestos. Radiographs were interpreted by a single National Institute of Safety and Health (NIOSH)-certified B-reader using the 1971 International Labor Office (ILO) Classification of the pneumoconioses as reference standard. Asbestosis was defined as an ILO coding of 1/0 or higher. Standardized Mortality Ratios (SMRs) were calculated using the general population of Ontario as reference.
Results: Among asbestos-cement workers without radiographic asbestosis at 20 years latency the lung cancer SMR was 3.84 (2.24-6.14). Among workers without asbestosis when examined at 25 years latency the SMR was 3.69 (1.59-7.26).
Conclusions: Workers from an Ontario asbestos-cement factory who did not have radiographic asbestosis at 20 or 25 years from first exposure to asbestos continued to have an increased risk of death from lung cancer during an additional 12 years of follow-up.

Vlastos, F. e.a. (2010)

Vlastos, F. e.a. (2010). Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma. J Thorac Oncol. 2009 Oct;4(10):1259-63.
Abstract
Introduction:
We report a survey of mesothelioma survival rates with insights into the survival benefit because of pemetrexed. We also studied a potential link between specific single nucleotide polymorphisms of transcobalamin II (TCII) gene and susceptibility to both asbestos and pemetrexed.
Methods: Clinical and occupational data from 287 consecutive mesothelioma patients were collected from the north-east region of France (1989-2007). Blood or paired tumoral and normal samples were collected from the last 210 French patients to study the TCII single nucleotide polymorphisms at the codon 259 (quantitative polymerase chain reaction). Results were compared with those obtained from a group of 263 French control healthy subjects and to a group of 91 German mesothelioma patients. Patients' characteristics and genotypes results were statistically analyzed for significant correlations. Results: The mean overall patient's survival was 18.19 +/- 21.07 months. Pemetrexed increased the patients' survival by 50% (21.81 versus 16.99 months). The TCII allele Proline (Pro) was overrepresented into the mesothelioma cohort when compared with the controls (35 versus 19.77%). This also concerned German patients. The alleles Pro and Proline Arginine (ProArg) were more frequent among patients exposed to asbestos (p = 0.005, p < 0.001, respectively). The allele ProArg was associated with the longest survival while under pemetrexed (p = 0.007). No difference was found in the genotypes of patients untreated with pemetrexed.
Conclusions: Pemetrexed treatment is related to a survival increase in mesothelioma patients. The allele Pro seems overrepresented in mesothelioma patients. Those having the allele ProArg present a better outcome under pemetrexed.

Wolf, A.S. e.a. (2010).

Wolf, A.S. e.a. (2010). Characteristics of malignant pleural mesothelioma in women. Ann Thorac Surg. 2010 Sep;90(3):949-56.
Abstract
Background:
The incidence of malignant pleural mesothelioma (MPM) is higher in men than in women, likely due to increased occupational asbestos exposure among men. Women also appear to experience better long-term survival. This study evaluates the role of gender in relation to established prognostic factors in MPM.
Methods: We reviewed 715 cases of MPM treated with extrapleural pneumonectomy at our institution between July 1987 and December 2008. Data for patients with epithelial and nonepithelial tumors were analyzed separately. Kaplan-Meier and Cox regression analyses were used to estimate survival for various cohorts to assess the relationship between gender and survival independent of age at surgery, stage, side, and preoperative laboratory studies.
Results: Of the 702 patients with complete data available, 114 out of 450 patients with epithelial tumors and 31 out of 252 patients with nonepithelial histology were women. Women with epithelial (and not nonepithelial) disease were found to differ significantly from men with respect to younger age, higher rate of thrombocytosis, and longer survival after surgery. The effect of gender on survival of patients with epithelial disease persisted when controlling for age, stage, thrombocytosis, leukocytosis, and anemia with a multivariable analysis. No significant differences in survival were seen among patients with nonepithelial disease with regard to gender, age, or anemia.
Conclusions: In the absence of other negative prognostic factors, women with epithelial MPM demonstrated a survival advantage. These findings support an aggressive approach to treating MPM including extrapleural pneumonectomy in individuals with favorable prognostic predictors, particularly women with epithelial histology and no other risk factors.

Kurata, S. e.a. (2010)

Kurata, S. e.a. (2010). Preliminary study of positron emission tomography/computed tomography and plasma osteopontin levels in patients with asbestos-related pleural disease. Jpn J Radiol. 2010 Jul;28(6):446-52.
Abstract
Purpose:
The aim of this study was to compare the results of semiquantitative analysis by(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) with plasma osteopontin levels in the same asbestos-related pleural disease population.
Materials and Methods: A total of 17 patients with asbestos-related pleural disease were prospectively recruited. They underwent PET/CT, and plasma osteopontin levels were measured. The maximum standardized uptake value (SUVmax) was determined from the most active pleural lesion in each patient.
Results: Malignant pleural mesothelioma (MPM) was histologically proven in 6 patients, and 11 patients had proven benign asbestos-related pleural diseases (7 pleural plaques, 4 asbestos pleurisy). Significant differences in SUVmax were found between patients with MPM and those with asbestos pleurisy (P = 0.031) and between patients with MPM and those with pleural plaques (P = 0.012). A significant difference was found in the plasma osteopontin levels between patients with asbestos pleurisy and patients with pleural plaques (Bonferroni correction, P = 0.024). The SUVmax in patients with benign asbestos-related diseases was statistically positively correlated with plasma osteopontin in the same group (Spearman's r = 0.75, P < 0.05).
Conclusion: PET/CT might be more helpful than plasma osteopontin for distinguishing benign asbestos-related pleural diseases from MPM, and the SUVmax in benign asbestos-related pleural diseases may reflect changes in pleural inflammation.

Vlastos, F. e.a. (2010)

Vlastos, F. e.a. (2010). Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma. J Thorac Oncol. 2009 Oct;4(10):1259-63.
Abstract
Introduction:
We report a survey of mesothelioma survival rates with insights into the survival benefit because of pemetrexed. We also studied a potential link between specific single nucleotide polymorphisms of transcobalamin II (TCII) gene and susceptibility to both asbestos and pemetrexed.
Methods: Clinical and occupational data from 287 consecutive mesothelioma patients were collected from the north-east region of France (1989-2007). Blood or paired tumoral and normal samples were collected from the last 210 French patients to study the TCII single nucleotide polymorphisms at the codon 259 (quantitative polymerase chain reaction). Results were compared with those obtained from a group of 263 French control healthy subjects and to a group of 91 German mesothelioma patients. Patients' characteristics and genotypes results were statistically analyzed for significant correlations. Results: The mean overall patient's survival was 18.19 +/- 21.07 months. Pemetrexed increased the patients' survival by 50% (21.81 versus 16.99 months). The TCII allele Proline (Pro) was overrepresented into the mesothelioma cohort when compared with the controls (35 versus 19.77%). This also concerned German patients. The alleles Pro and Proline Arginine (ProArg) were more frequent among patients exposed to asbestos (p = 0.005, p < 0.001, respectively). The allele ProArg was associated with the longest survival while under pemetrexed (p = 0.007). No difference was found in the genotypes of patients untreated with pemetrexed.
Conclusions: Pemetrexed treatment is related to a survival increase in mesothelioma patients. The allele Pro seems overrepresented in mesothelioma patients. Those having the allele ProArg present a better outcome under pemetrexed.

Moore, S. e.a. (2010)

Moore, S. e.a. (2010). Living with mesothelioma. A literature review. Eur J Cancer Care (Engl). 2010 Jul;19(4):458-68. Abstract
Mesothelioma is an asbestos-related cancer that affects mainly the pleura. World-wide incidence is increasing and set to rise for some time particularly in developing countries. Mesothelioma is uniformly fatal and often associated with difficult symptoms. The purpose of this review is to identify what is known about the experience of people living with mesothelioma. A literature search identified 13 papers covering qualitative studies, patient-reported quality of life data collected as part of a clinical trial, symptoms and survey of patients and carers. The findings suggest the impact of mesothelioma is multidimensional on: physical symptoms (especially pain, breathlessness, fatigue, cough, sleep disturbance, appetite loss and sweating), emotional functioning (anxiety, depression, fear and isolation), social consequences (changes in roles and relationships) and interventions (the necessity of frequent anti-cancer treatments and admissions for symptom control). The impact on family members is significant also. Although limited, these findings provide an important insight into the impact of mesothelioma on patients and family members and suggest areas where service provision may fail to meet their needs. Finally, the review highlights an urgent need for further research to more fully understand the experience of living with mesothelioma and identify the specific needs of patients and family members.

Marinaccio, A. e.a. (2010).

Marinaccio, A. e.a. (2010). Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med. 2010 Nov;67(11):760-5.
Abstract
Objectives:
The epidemiology of extrapleural malignant mesothelioma is rarely discussed and the risk of misdiagnosis and the very low incidence complicate the picture. This study presents data on extrapleural malignant mesothelioma from the Italian National Mesothelioma Register (ReNaM).
Methods: ReNaM works on a regional basis, searching for cases and interviewing subjects to investigate asbestos exposure. Classification and code criteria for certainty of diagnosis and exposure modalities are set by national guidelines. Between 1993 and 2004, 681 cases were collected. Incidence measures and exposure data refer to the ReNaM database. Age-standardised rates were estimated by the direct method using the Italian resident population in 2001. Correlations between the incidence of pleural and non-pleural malignant mesothelioma for the 103 Italian provinces were analysed.
Results: Standardised incidence rates (Italy, 2004, per million inhabitants) were 2.1 and 1.2 cases for the peritoneal site (in men and women, respectively), 0.2 cases for the tunica vaginalis testis, and 0.1 in the pericardial site, varying widely in different parts of the country. Mean age at diagnosis for all extrapleural malignant mesothelioma cases was 64.4 years and the men/women ratio was 1.57:1. Median latency was over 40 years for all extrapleural sites combined. The correlation between pleural and peritoneal mesothelioma was 0.71 (Pearson's r coefficient, p<0.001). Modalities of exposure to asbestos fibres were investigated for 392 cases.
Conclusions: The rarity of the disease, the low specificity of diagnosis and difficulties in identifying the modalities of asbestos exposure call for caution in discussing aetiological factors other than asbestos.

Mirabelli, D. e.a. (2010)

Mirabelli, D. e.a. (2010). Non-occupational exposure to asbestos and malignant mesothelioma in the Italian National Registry of Mesotheliomas. Occup Environ Med. 2010 Nov;67(11):792-4. Abstract
Background:
Malignant mesotheliomas are strictly related to asbestos, but in a proportion of cases no exposure can be recalled. Published estimates of this proportion have important variations. Historical and geographical differences in the fraction of cancer due to any given exposure are to be expected, but incomplete identification of non-occupational exposures may have played a role.
Methods: To assess the role of non-occupational exposures in causing malignant mesotheliomas in Italy, the exposures of cases registered by the national mesothelioma registry (ReNaM) were examined. ReNaM started in 1993 in five regions and currently covers 98% of the Italian population. Information on occupational and non-occupational exposures of cases is collected whenever possible.
Results: From 1993 to 2001 ReNaM registered 5173 malignant mesothelioma cases, and exposures were assessed in 3552 of them. 144 and 150 cases with exposures limited to environmental (living in the neighbourhood of an industrial or natural source of asbestos) or familial (living with a person occupationally exposed to asbestos) circumstances, respectively, were identified, accounting for 8.3% of all cases.
Conclusions: Geographical variations in the proportion of cases due to non-occupational exposures may be explained by the past distribution of asbestos-using industries.

Lotti, M. (e.a.)

Lotti, M. (e.a.). Occupational toxicology of asbestos-related malignancies. Clin Toxicol. 2010 Jul;48(6):485-96.
Abstract
Introduction:
Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies.
Methods: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included.
Assessment of exposure: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements.
Screening for malignancies: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing.
Attribution of lung cancer: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits.
Mesothelioma: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. Conclusions: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.

McDonald, J.C. (2010)

McDonald, J.C. 2010). Epidemiology of malignant mesothelioma--an outline. Ann Occup Hyg. 2010 Nov;54(8):851-7.
Abstract

In the 1960s and 1970s, well designed case-referent studies put beyond doubt that exposure to airborne asbestos fibres was a cause of malignant mesothelioma. Some 35 cohort mortality studies in a large variety of industries during the 20-year period, 1974-1994, showed a wide range of outcomes, but in general that the risk was higher in exposures which included amphiboles rather than chrysotile alone. Real progress began, however, with discoveries along several lines: the link between pleural changes and mineralogy, the concept and importance of biopersistence, the developments in counting and typing mineral fibres in lung tissue, and data on amphibole mining in South Africa and Australia for comparison with that on chrysotile in Canada and Italy. This led to the recognition of the potential contamination in North America of chrysotile with tremolite. A survey in Canada in 1980-1988 and other surveys demonstrated that crocidolite, amosite, and tremolite could explain almost all cases of mesothelioma. Effective confirmation of this was finally achieved with data on vermiculite miners in Libby, Montana, in the years 1983-1999, where exposure was to tremolite-actinolite and/or other amphibole fibres alone.

Harding, A.E. & Darnton, A.J. (2010)

Harding, A.E. & Darnton, A.J. (2010). Asbestosis and mesothelioma among British asbestos workers (1971-2005). Am J Ind Med. 2010 Nov;53(11):1070-80.
Abstract
Background:
Ascertainment of asbestosis and mesothelioma from underlying cause of death underestimates the burden of these diseases. The aims of this study were to estimate the true frequency of asbestosis and mesothelioma among asbestos workers in Great Britain (GB), and to identify factors associated with the risk of death with these diseases.
Methods: The GB Asbestos Survey was established in 1971 to monitor long-term health outcomes among workers covered by regulations to control asbestos at work. Asbestosis and mesothelioma cases were defined by multiple cause of death, and were ascertained by identifying asbestos workers on the GB Asbestosis and Mesothelioma Registers. Standardized mortality ratios (SMRs) were calculated; the risks of asbestosis and mesothelioma were modeled with Poisson regression analysis. Deaths to the end of 2005 were included.
Results: There were 15,557 deaths between 1971 and 2005 among the 98,912 workers. Altogether 477 asbestosis and 649 mesothelioma cases were identified. The SMR for all causes was 1.42, for asbestosis 51.3, and for mesothelioma 13.5. In multiply adjusted analysis, age, sex, job, and birth cohort were significantly associated with asbestosis and mesothelioma. For asbestosis year of first exposure, and for mesothelioma latency, were also statistically significant.
Conclusions: The asbestos workers experienced high mortality from all causes, asbestosis, and mesothelioma. There was some evidence that the risk of asbestosis and mesothelioma was lower in later birth cohorts and among those first occupationally exposed to asbestos more recently. Due to the long latency of both diseases, further follow-up is required to confirm these trends.

Rolland, P. e.a. (2010)

Rolland, P. e.a. (2010). Occupations and industries in France at high risk for pleural mesothelioma: A population-based case-control study (1998-2002). Am J Ind Med. 2010 Dec;53(12):1207-19.
Abstract
Background:
Occupational exposure to asbestos, widely used in various industries for decades, is the most important risk factor for pleural mesothelioma. We report here the ranking of occupations and industries in France at high risk for this cancer among men and women.
Methods: A population-based case-control study, conducted from 1998 to 2002, included 462 cases (80.3% men) and 897 controls. Data were collected in face-to-face interviews with a standardized questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each occupation and industry; subjects never employed in each category were the reference.
Results: For men, risks were high for several occupations and industries. Besides the expected high risks for non-metallic mineral product makers and manufacturing asbestos products, occupations such as plumbers (OR = 5.57, 95% CI: 2.90-10.69), sheet-metal workers, welders, metal molders, coremakers, and cabinetmakers were also at high risk. Elevated risks were found in the industries of shipbuilding (OR = 9.13, 95% CI: 5.20-16.06) and construction, but also in the manufacturing of metal products, chemicals, and railroad and aircraft equipment. The results for women showed increased but not significant risks in several occupational activities.
Conclusions: This report provides new insight into the epidemiology of mesothelioma, confirming risks for occupational activities reported earlier and pointing out risks in activities never previously reported. It offers guidance to authorities for the compensation of asbestos victims and for prevention in at-risk activities still involving asbestos-containing products.

Fujimoto, N. e.a. (2010)

Fujimoto, N. e.a. (2010). Clinical investigation of malignant mesothelioma in Japan. J Cancer Res Clin Oncol. 2010 Nov;136(11):1755-9.
Abstract
Purpose:
The asbestos-related problems caused much social concern; however, no large-scale study was conducted about clinical features of MM in Japan. Patients with MM who have a history of occupational asbestos exposure (AE) are provided worker's compensation in Japan. However, only about 10% of MM cases were actually claimed and compensated. So there is still controversy over the association between MM and AE. The aim of this study is to investigate the clinical features of MM. We also aimed to clarify the association between MM and occupational AE in Japan.
Methods: We examined the clinical features of MM cases. Clinical information was obtained including gender, age, site of origin, pathological subtype, radiological findings, and treatment outcome. To investigate the association between MM and AE, investigators interviewed all patients regarding work and residential history.
Results: Between January 2005 and December 2007, 105 cases (median age: 63 years, range 35-80, male/female: 88/17) were diagnosed with MM in the Rosai Hospital group and related facilities. Among them, 94(89.5%) cases originated in the pleura, 7(6.7%) in the peritoneum, 2(1.9%) in the pericardium, and 1(0.9%) in the tunica vaginalis testis. There were 69(65.7%) epithelioid, 19(18.1%) biphasic, 16(15.2%) sarcomatoid, and 1 unclassified pathological subtypes of MM. A favorable survival rate was indicated in the patient group of MPM that underwent surgery compared to others, though it was not statistically significant (P = 0.1743). The occupational AE was indicated in 89 cases (84.8%). Three patients had no history of occupational AE, but lived with someone who was in an occupation that handled asbestos. There were two patients in which AE was indicated in their life environment. Altogether, AE was indicated in 93(88.6%) patients.
Conclusions: This study stresses the urgent need for physicians to acknowledge the association between MM and AE, and to inquire thoroughly regarding AE to the patients with MM.

Yano, E. e.a. (2010)

Yano, E. e.a. (2010). Lung cancer mortality from exposure to chrysotile asbestos and smoking: a case-control study within a cohort in China. Occup Environ Med. 2010 Dec;67(12):867-71. Abstract
Objective:
To confirm the association between exposure to chrysotile asbestos and lung cancer risk and to demonstrate the combined effect of smoking and asbestos exposure.
Methods: A case-control study of 1139 asbestos workers identified 41 male lung cancer cases in 2001; each case was matched by age (±5 years) with five controls. Workers in seven workshops were categorised into high-, medium- and low-exposure subgroups, and conditional logistic regression was applied to estimate the odds ratios for lung cancer risk associated with the different exposure levels. Smoking, age at first exposure, and exposure duration were considered as covariates/confounding factors. A joint effect of asbestos exposure and smoking on lung cancer risk was analysed using a conditional logistical model.
Results: 54% of cases had high exposure and 24% low exposure, while 24% of controls had high exposure and 44% low exposure. Smoking was more common in cases (90%) than in controls (73%). The adjusted OR for lung cancer was 3.66 (95% CI 1.61 to 8.29) for high exposure and was elevated slightly for medium exposure (1.25; 95% CI 0.47 to 3.31). Smoking was related to lung cancer risk (OR 3.33; 95% CI 1.10 to 10.08). In comparison with the low-exposure non-smoking group, the OR for the high-exposure smoking group was 10.39 (1.34 to 82.45), in contrast to 5.23 (0.50 to 54.58) for high-exposure non-smoking workers.
Conclusions: These results confirm the strong association between exposure to chrysotile asbestos and lung cancer risk, and support an interactive effect of asbestos exposure and smoking which is more than additive.

Frost, G. e.a. (2011).

Frost, G. e.a. (2011). The effect of smoking on the risk of lung cancer mortality for asbestos workers in Great Britain (1971–2005). Ann Occup Hyg , doi: 10.1093/annhyg/meq089 . First published online: January 20, 2011.
Abstract
Objectives:
Workers in the asbestos industry tend to have high smoking rates compared to the general population. Both asbestos exposure and cigarette smoking are recognized risk factors for lung cancer mortality, but the exact nature of the interaction between the two remains uncertain. The aim of this study was to examine the effect of smoking and smoking cessation among asbestos workers in Great Britain (GB) and investigate the interaction between asbestos exposure and smoking.
Methods: The study population consisted of 98 912 asbestos workers recruited into the GB Asbestos Survey from 1971, followed-up to December 2005. Poisson regression was used to estimate relative risks of lung cancer mortality associated with smoking habits of the asbestos workers and to assess whether these effects differed within various categories of asbestos exposure. The interaction between asbestos exposure and smoking was examined using the Synergy (S) and Multiplicativity (V) indices, which test the hypotheses of additive and multiplicative interaction, respectively. The proportion of lung cancers among smokers attributable to the interaction of asbestos and smoking was also estimated.
Results: During 1 780 233 person-years of follow-up, there were 1878 deaths from lung cancer (12% of all deaths). Risk of lung cancer mortality increased with packs smoked per day, smoking duration, and total smoke exposure (pack-years). Asbestos workers who stopped smoking remained at increased risk of lung cancer mortality up to 40 years after smoking cessation compared to asbestos workers who never smoked. The effects of smoking and stopping smoking did not differ by duration of asbestos exposure, main occupation, age at first asbestos exposure, year of first exposure, or latency period. The interaction between asbestos exposure and smoking for asbestos workers was greater than additive [S 1.4, 95% confidence interval (CI) 1.2–1.6], and the multiplicative hypothesis could not be rejected (V 0.9, 95% CI 0.3–2.4). For those asbestos workers who smoked, an estimated 26% (95% CI 14–38%) of lung cancer deaths were attributable to the interaction of asbestos and smoking.
Conclusions: This study emphasizes the importance of smoking prevention and cessation among those who work in the asbestos industry.

Haber & Haber (2010)

Haber & Haber (2010). Malignant Mesothelioma: A Clinical Study of 238 Cases. Industrial Health. 2010 Dec 16.
Abstract
Malignant mesothelioma is a diffuse tumor arising in the pleura, peritoneum, or other serosal surface and is closely associated with asbestos exposure. An estimated 2,500 to 3,000 cases are diagnosed each year in the United States. Although there are individual case reports and small series detailing the clinical aspects of mesothelioma, few studies examine a large series of patients with malignant mesothelioma from the clinical perspective. This study reports on the findings of 238 cases of malignant mesothelioma from a private consultative medical practice. Most cases had a history of occupational asbestos exposure. The mean latency was 48.5 yr, with women having a longer latency than men. The mean age at diagnosis was 70. Survival overall was poor (mean 8.8 months), but treatment was beneficial (mean 11.3 versus 6.4 months). Epithelioid histology conferred a survival advantage over sarcomatoid and responded better to treatment. Our data support an inverse relationship between asbestos dose and latency.

Zucali e.a. (2011)

Zucali e.a. (2011). Advances in the biology of malignant pleural mesothelioma. Cancer Treat Rev. 2011 Jan 31.
Abstract
Malignant pleural mesothelioma is a highly aggressive cancer with a very poor prognosis. Although the mechanism of carcinogenesis is not fully understood, approximately 80% of malignant pleural mesothelioma can be attributed to asbestos fiber exposure. This disease is largely unresponsive to conventional chemotherapy or radiotherapy, and most patients die within 10-17months of their first symptoms. Currently, malignant pleural mesothelioma therapy is guided by clinical stage and patient characteristics rather than by the histological or molecular features of the tumor. Several molecular pathways involved in malignant pleural mesothelioma have been identified; these include cell cycle regulation, apoptosis, growth factor pathways, and angiogenesis. Unfortunately, several agents targeting these processes, including erlotinib, gefitinib, and imatinib, have proven ineffective in clinical trials. A greater understanding of the molecular pathways involved in malignant pleural mesothelioma is needed to develop better diagnostics, therapeutics, and preventative measures. Moreover, understanding the biological basis of mesothelioma progression may facilitate personalized treatment approaches, and early identification of poor prognostic indicators may help reduce the heterogeneity of the clinical response. This paper reviews advances in the molecular biology of malignant pleural mesothelioma in terms of pathogenesis, the major molecular pathways and the associated therapeutic strategies, and the roles of biomarkers.

Greillier e.a. (2011)

Greillier e.a. (2011). Targeted therapies in malignant pleural mesothelioma: a review of clinical studies. Anticancer Drugs. 2011 Mar;22(3):199-205.
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose exposure to asbestos fibers is the main etiology. The incidence of MPM is anticipated to increase worldwide during the first half of this century. MPM is notoriously refractory to most treatments, and the only standard of care is cisplatin and antifolate first-line chemotherapy. The urgent need for additional therapeutic agents, in parallel with advances in the knowledge of the molecular events of oncogenesis, has resulted in the development of the so-called 'targeted agents' that specifically inhibit critical pathways in malignant cells and in their microenvironment. We carried out a comprehensive review of the literature from January 2000 to May 2010 on studies that assessed targeted agents for the systemic treatment of MPM. Although tyrosine kinase inhibitors directed against the epidermal growth factor and the platelet-derived growth factor receptors did not show significant clinical activity in phase II studies, some other targeted therapies seemed promising, notably histone deacetylase inhibitors and antiangiogenic agents. However, none of these has yet reached daily practice. That is the reason why efforts must continue in the area of clinical and translational research for MPM.

Hoda, M.A. e.a. (2011)

Hoda, M.A. e.a. (2011). Temsirolimus inhibits malignant pleural mesothelioma growth in vitro and in vivo: synergism with chemotherapy. J Thorac Oncol. 2011 May;6(5):852-63.
Abstract
Introduction:
Human malignant pleural mesothelioma (MPM) is an asbestos-related malignancy characterized by frequent resistance to chemotherapy and radiotherapy. Here, we investigated the feasibility of mammalian target of rapamycin (mTOR) inhibition by temsirolimus as an antimesothelioma strategy.
Methods: Phosphorylation of mTOR (p-mTOR) was assessed by immunohistochemistry in MPM surgical specimens (n = 70). Activation of mTOR and impact of mTOR inhibition by temsirolimus was determined in MPM cell lines in vitro (n = 6) and in vivo as xenografts in severe combined immunodeficiency mice (n = 2) either as single agent or in combination with cisplatin.
Results: Strong immunoreactivity for p-mTOR was predominantly detected in epitheloid and biphasic but not sarcomatoid MPM specimens while adjacent normal tissues remained widely unstained. Accordingly, all mesothelioma cell lines harbored activated mTOR, which was further confirmed by hyperphosphorylation of the downstream targets pS6K, S6, and 4EBP1. Temsirolimus potently blocked mTOR-mediated signals and exerted a cytostatic effect on mesothelioma cell lines in vitro cultured both as adherent monolayers and as nonadherent spheroids. Mesothelioma cells with intrinsic or acquired cisplatin resistance exhibited hypersensitivity against temsirolimus. Accordingly, cisplatin and temsirolimus exerted synergistic inhibition of the mTOR downstream signals and enhanced growth inhibition and/or apoptosis induction in mesothelioma cell lines. Finally, temsirolimus was highly active against MPM xenograft models in severe combined immunodeficiency mice both as a single agent and in combination with cisplatin.
Conclusion: The mTOR inhibitor temsirolimus is active against mesothelioma in vitro and in vivo and synergizes with chemotherapy. These data suggest mTOR inhibition as a promising novel therapeutic strategy against MPM.

Bij, S. van de e.a. (2011)

Bij, S. van de e.a. (2011). Markers for the non-invasive diagnosis of mesothelioma: a systematic review. Br J Cancer. 2011 Apr 12;104(8):1325-33.
Abstract
Background: Numerous markers have been evaluated to facilitate the non-invasive diagnostic work-up of mesothelioma. The purpose of this study was to conduct a structured review of the diagnostic performance of non-invasive marker tests for the detection of mesothelioma in patients with suspected mesothelioma.
Methods: Studies on the diagnostic accuracy of serum and cytological markers published till 31 December 2009, available in either PUBMED or Embase, to detect or exclude the presence of mesothelioma were extracted. Study quality was assessed with use of the Quadas criteria.
Results: In total, 82 articles were included in this systemic review. Overall, quality of the incorporated studies to address our objective was poor. The most frequently studied immunohistochemical markers for cytological analysis were EMA, Ber-Ep4, CEA, and calretinin. The most frequently investigated serum marker was soluble mesothelin-related protein (SMRP). The markers CEA, Ber-EP4, and calretinin were most valuable in discriminating mesothelioma from other malignant diseases. Markers EMA and SMRP were most valuable in discriminating mesothelioma from non-malignant diseases. No marker performed well in discriminating between mesothelioma and all other diseases.
Conclusion: Currently, there is only limited evidence to properly assess the value of non-invasive marker tests in the diagnosis of mesothelioma. Studies were of limited value to address our objective and results showed considerable unexplained study heterogeneity.

Kao, S.C.H e.a. (2011)

Kao, S.C.H e.a. (2011). Molecular biomarkers in malignant mesothelioma: state of the art. Pathology. 2011 Apr;43(3):201-12.
Abstract
Malignant mesothelioma (MM) is an aggressive tumour affecting the mesothelial surfaces of the pleural and peritoneal cavities and, rarely, the pericardium and the tunica vaginalis testis. Despite a ban of asbestos in many industrialised nations, the present high incidence of MM is expected to continue, due to the long latency period between first asbestos exposure and occurrence of disease, making it an important health issue for the future. The diagnosis of MM can be difficult, both from a clinical and pathological perspective. It is not unusual for patients to undergo several medical investigations without definitive diagnosis early in their course of illness. Understandably, there is intense interest in the discovery of markers that can be assessed in pleural effusions, histological specimens, and serum to assist with the difficult early diagnosis of MM. Considering the primary aetiological role of asbestos, there is theoretically an easily identifiable target population for screening with a biomarker with adequate sensitivity and specificity or with a combination of biomarkers. In this review we focus on biomarkers that have been examined in the setting of either early diagnosis of MM in symptomatic patients or screening of asbestos-exposed individuals.

Campbell, N.P. & Kindler, H.L. (2011)

Campbell, N.P. & Kindler, H.L. (2011). Update on malignant pleural mesothelioma. Semin Respir Crit Care Med. 2011 Feb;32(1):102-10. Abstract
Malignant pleural mesothelioma is an aggressive cancer principally attributable to asbestos. Although the incidence is now declining in the United States, it will continue to increase worldwide until all nations institute regulations limiting asbestos use and exposure. This is a heterogeneous disease, with three pathological subtypes that yield very different outcomes. Stage is less important than histology in determining prognosis. The biomarkers serum mesothelin-related peptide and osteopontin are being evaluated for screening asbestos-exposed individuals and monitoring disease response. The optimal surgical procedure remains controversial because extrapleural pneumonectomy and pleurectomy/decortication can achieve similar results. The reference chemotherapy regimen, pemetrexed-cisplatin, improves survival and quality of life. Key questions about maintenance therapy and the optimal regimens for elderly and frail patients remain to be answered. Although few other cytotoxic drugs have activity, a surprising number of novel agents are being investigated.

Carbone, M. e.a. (2011)

Carbone, M. e.a. (2011). Malignant mesothelioma: Facts, myths and hypotheses. J Cell Physiol. 2011 Mar 16. doi: 10.1002/jcp.22724. Abstract
Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM.

Marinaccio, A. e.a. (2011)

Marinaccio, A. e.a. (2011). Pleural malignant mesothelioma epidemic. Incidence, modalities of asbestos exposure and occupations involved from the italian national register. Int J Cancer. 2011 Jun 6. doi: 10.1002/ijc.26229.
Abstract
Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992) a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004 a case-list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardised incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N = 4,577 cases), while 4.4% was due to cohabitation with someone (generally the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers the median year of first exposure was 1957 and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signalled as "at risk" (asbestos-cement industry, shipbuilding and repair, railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all-too-predictable asbestos effects should be transferred to developing countries where asbestos use is spreading. .

Reid, A. e.a. (2011)

Reid, A. e.a., (2011). Does exposure to asbestos cause ovarian cancer? A systematic literature review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2011 May 24. 1.
Abstract
The asbestos and ovarian cancer relationship is not well understood because of small numbers of women exposed to asbestos, small numbers of cases and misclassification of peritoneal mesothelioma as ovarian cancer on death certificates. The aim is to conduct a meta-analysis to quantify the evidence that exposure to asbestos causes ovarian cancer. Fourteen cohort and two case-control studies were identified in medline searches from 1950-2008. Statistically significant excess mortality was reported in four of the cohort studies, all of which determined their outcomes from the death certificate. Peritoneal mesotheliomas were reported in these studies, two of which re-examined pathology specimens and reported disease misclassification. Exposure-response relationships were inconsistent. When all studies were included in a meta-analysis, the effect size was 1.75 (95%CI 1.45-2.10) attenuating to 1.29 (95%CI 0.97-1.73) in studies with confirmed ovarian cancers. Taken without further analysis, women thought to have ovarian cancer had an increased rate in the meta-analysis if reporting having been exposed to asbestos, compared with reference populations. This result may have occurred because of disease misclassification.

Kielkowski, D. e.a. (2011)

Kielkowski, D. e.a. (2011). Trends in mesothelioma mortality rates in South Africa: 1995-2007. Occup Environ Med. 2011 Jul;68(7):547-9. Abstract
Objective In 1984, South Africa had one of the highest mesothelioma rates in the world. The objective of this analysis was to calculate mesothelioma mortality rates in the South African population from 1995 to 2007. Methods Annual mortality data and midyear population estimates were used to compute mortality rates by age group and gender for each year. The WHO World Standard Population was used as the reference population to calculate age-adjusted rates. Poisson regression models were used to test for trends. Results In total, 2509 deaths due to mesothelioma were identified in the study period: 1920 in men and 588 in women. There were no significant trends in mesothelioma mortality rates: age-adjusted mortality rates fluctuated from 11 to 16 and from 3 to 5 per million per year for men and women, respectively. Conclusion These mortality rates are much lower than expected, given the historical production and use of, and high exposure to, asbestos in South Africa. Possible reasons for this are discussed, including the effect of HIV which has been instrumental in reducing the life expectancy of South Africans in the last two decades. Asbestos-exposed individuals may not live long enough to develop mesothelioma. Competing causes of death need to be taken into account when constructing models to predict mesothelioma mortality rates.

Clin, B. e.a. (2011).

Clin, B. e.a. (2011). Cancer incidence within a cohort occupationally exposed to asbestos: a study of dose-response relationships. Occup Environ Med. 2011 Mar 15.
Abstract
Objectives
The aim of our study was to analyse the dose-response relationship between occupational asbestos exposure and risk of cancer.
Methods Our study was a retrospective morbidity study based on 2024 subjects occupationally exposed to asbestos, conducted over the period 1 January 1978 to 31 December 2004. Analysis of the dose-response relationship between occupational asbestos exposure, as a time-dependant variable, and risk of cancer was performed using a Cox model. In order to account for the effect of latency, we conducted the analysis with a lag of 10 years.
Results 285 cases of cancers were observed in our cohort. The relative risk of pleuro-peritoneal mesothelioma, lung cancer and colorectal cancer associated with asbestos exposure, adjusted for age as a time-dependant variable and for sex, was correlated with exposure intensity (or average exposure level, AEL). The risk of cancer, whatever the anatomical site, did not increase with the duration of exposure to asbestos.
Conclusion While confirming the established relationship between asbestos exposure and pleuropulmonary and peritoneal cancers, this study also suggests a causal relationship between asbestos exposure and colorectal cancer.

Chapman, E.A. e.a. (2011)

Chapman, E.A. e.a. (2011). Breath analysis in asbestos-related disorders: a review of the literature and potential future applications. J Breath Res. 2010 Sep;4(3):034001.
Abstract
Asbestos usage was very common worldwide in the last century and continues in several countries today. Several diseases occur due to asbestos exposure, including malignant tumours such as malignant mesothelioma of the pleura and lung cancer, which have a very poor prognosis. Asbestos inhalation may also result in more benign conditions such as asbestosis (or pulmonary fibrosis due to asbestos), pleural plaques and pleural thickening. It is predicted that asbestos-associated mortality and morbidity will continue to increase, but methods for diagnosing asbestos-related disease are currently invasive and unsuitable for an increasingly elderly population. New non-invasive methods such as analysis of exhaled breath biomarkers e.g. exhaled nitric oxide (F(E)NO), exhaled breath condensate or of exhaled volatile organic compounds could potentially be extremely useful in these conditions. This article reviews the current literature on this topic and suggests areas for their application in the future.

Jamrozik, E. e.a. (2011)

Jamrozik, E. e.a. (2011). Asbestos-related disease. Intern Med J. 2011 May;41(5):372-80. doi: 10.1111/j.1445-5994.2011.02451.x.
Abstract
Inhalation of airborne asbestos fibres causes several diseases. These include asbestosis, lung cancer, malignant mesothelioma as well as pleural effusion, discrete (plaques) or diffuse benign pleural fibrosis and rolled atelectasis. The lag time between exposure and the development of disease may be many decades, thus the health risks of asbestos continue to be relevant despite bans on the use of asbestos and improvements in safety regulations for those who are still exposed. Asbestos was mined and used extensively in Australia for over 100 years and Australia is now experiencing part of a worldwide epidemic of asbestos-related disease. This review provides insight into the history and epidemiology of asbestos-related disease in Australia and discusses relevant clinical aspects in their diagnosis and management. The past and current medico-legal aspects of asbestos as well as currently evolving areas of research and future projections are summarized.

Wang, X.R. e.a. (2011)

Wang, X.R. e.a. (2011). Cancer mortality among Chinese chrysotile asbestos.
Abstract
To determine mortality associated with exposure to chrysotile asbestos, a cohort of asbestos workers from an asbestos textile factory in China was followed prospectively from 1972 to 2008. A total 577 workers were successfully followed, achieving a follow-up rate of 98.5% over 37 years. Employment data and smoking information were obtained from factory and individual workers. Vital status was ascertained from factory personnel records and the municipal death registry. Workers were categorized into high, medium and low exposure groups in terms of their job titles and workshops. Follow-up generated 17,508 person-years, with 259 deaths from all causes, 96 all cancers and 53 lung cancers and 2 mesotheliomas. The highest cancer mortality was observed in the high exposure group, with 1.5-fold age-adjusted mortality from all cancers and 2-fold from lung cancer compared to the low exposure group. Age and smoking adjusted hazard ratio in the high exposure group was 2.99 (95%CI, 1.30, 6.91) for lung cancer and 2.04 (1.12, 3.71) for all cancers. Both smokers and nonsmokers at the high exposure level had a high death risk of lung cancer, with a clearer exposure-response trend seen in smokers. This study confirmed increased mortality from lung cancer and all cancers in asbestos workers, and the cancer mortality was associated with exposure level. textile workers. Lung Cancer. 2011 Jul 26.

Zeig Owens, R. e.a. (2011)

Zeig Owens, R. e.a. (2011). Early assessment of cancer outcomes in New York City firefighters after the 9/11 attacks: an observational cohort study. The Lancet , Volume 378, Issue 9794, 3-9 September 2011, Pages 898-905.
Summary
Background
The attacks on the World Trade Center (WTC) on Sept 11, 2001 (9/11) created the potential for occupational exposure to known and suspected carcinogens. We examined cancer incidence and its potential association with exposure in the first 7 years after 9/11 in firefighters with health information before 9/11 and minimal loss to follow-up.
Methods
We assessed 9853 men who were employed as firefighters on Jan 1, 1996. On and after 9/11, person-time for 8927 firefighters was classified as WTC-exposed; all person-time before 9/11, and person-time after 9/11 for 926 non-WTC-exposed firefighters, was classified as non-WTC exposed. Cancer cases were confirmed by matches with state tumour registries or through appropriate documentation. We estimated the ratio of incidence rates in WTC-exposed firefighters to non-exposed firefighters, adjusted for age, race and ethnic origin, and secular trends, with the US National Cancer Institute Surveillance Epidemiology and End Results (SEER) reference population. CIs were estimated with overdispersed Poisson models. Additional analyses included corrections for potential surveillance bias and modified cohort inclusion criteria.
Findings
Compared with the general male population in the USA with a similar demographic mix, the standardised incidence ratios (SIRs) of the cancer incidence in WTC-exposed firefighters was 1•10 (95% CI 0•98–1•25). When compared with non-exposed firefighters, the SIR of cancer incidence in WTC-exposed firefighters was 1•19 (95% CI 0•96–1•47) corrected for possible surveillance bias and 1•32 (1•07–1•62) without correction for surveillance bias. Secondary analyses showed similar effect sizes.
Interpretation
We reported a modest excess of cancer cases in the WTC-exposed cohort. We remain cautious in our interpretation of this finding because the time since 9/11 is short for cancer outcomes, and the reported excess of cancers is not limited to specific organ types. As in any observational study, we cannot rule out the possibility that effects in the exposed group might be due to unidentified confounders. Continued follow-up will be important and should include cancer screening and prevention strategies.

Tomioka, K. e.a. (2011)

Tomioka, K. e.a. (2011). An updated historical cohort mortality study of workers exposed to asbestos in a refitting shipyard, 1947-2007. Int Arch Occup Environ Health. 2011 Jun 9.
Abstract
Purpose:
To evaluate the long-term health effects of occupational asbestos exposure, an updated historical cohort mortality study of workers at a refitting shipyard was undertaken. Methods: The cohort consisted of 249 male ship repair workers (90 laggers, 159 boiler repairers). To determine relative excess mortality, standardized mortality ratios (SMRs) were calculated using mortality rates among the Japanese male population. Mortality follow-up of study subjects was performed for the period from 1947 till the end of 2007.
Results: We identified the vital status of 87 (96.7%) laggers and 150 (94.3%) boiler repairers. Of these, 63 (72.4%) and 95 (63.3%), respectively, died. Laggers, who had handled asbestos materials directly, showed a significantly elevated SMR of 2.64 (95% confidence interval [CI]: 1.06-5.44) for lung cancer and 2.49 (95% CI: 1.36-4.18) for nonmalignant respiratory diseases. Boiler repairers, who had many opportunities for secondary exposure to asbestos and a few for direct exposure, showed no significant elevation in SMR for lung cancer but a significantly elevated SMR of 1.78 (95% CI: 1.06-2.81) for nonmalignant respiratory diseases. In an analysis according to duration of employment, there was a significantly elevated SMR of nonmalignant respiratory diseases in the longer working years group. Among workers from both jobs, no deaths caused by mesothelioma in addition to those in the original study were found and no subject died from larynx cancer.
Conclusion: This updated study confirmed a significant excess of asbestos-related mortality from diseases such as lung cancer and nonmalignant respiratory diseases among workers in a refitting shipyard in Japan.

Kanarek M.S (2011)

Kanarek M.S (2011). Mesothelioma from chrysotile asbestos: update. Ann Epidemiol. 2011 Sep;21(9):688-97.
Abstract
Purpose:
There are different mineral classes of asbestos, including serpentines and amphiboles. Chrysotile is the main type of serpentine and by far the most frequently used type of asbestos (about 95% of world production and use). There has been continuing controversy over the capability of chrysotile asbestos to cause pleural and peritoneal mesothelioma. This review is to help clarify the issue by detailing cases and epidemiology studies worldwide where chrysotile is the exclusive or overwhelming fiber exposure.
Methods: A worldwide literature review was conducted of asbestos and associated mesothelioma including case series, case-control and cohort epidemiology studies searching for well documented chrysotile asbestos associated mesothelioma cases.
Results: Chrysotile asbestos exposures have occurred in many countries around the world from mining, manufacturing and community exposures. There have been many documented cases of mesothelioma from those exposures.
Conclusions: Chrysotile asbestos, along with all other types of asbestos, has caused mesothelioma and a world-wide ban of all asbestos is warranted to stop an epidemic of mesothelioma.

Hanley, A. e.a. (2011)

Hanley, A. e.a. (2011). Mortality trends in asbestosis, extrinsic allergic alveolitis and sarcoidosis in England and Wales. Respir Med. 2011 Sep;105(9):1373-9.
Abstract
Background:
To ascertain the trends in mortality from Asbestosis, Extrinsic Allergic Alveolitis (EAA) and Sarcoidosis in England and Wales, we analysed mortality data from the Office of National Statistics.
Methods: We calculated age and stratum specific mortality rates between 1968 and 2008 and applied these to the 2008 population to generate annual standardised expected number of deaths. Poisson regression was used to calculate annual mortality rate ratios.
Results: From 1968 to 2008 there were 1958 registered deaths from Asbestosis, 878 deaths from EAA and 3544 deaths from Sarcoidosis. The Asbestosis mortality rate increased from 0.04 (95% CI 0.03-0.05) in the 1968-1972 calendar period to 0.12 (95% CI 0.10-0.13) in the 2005-2008 period whist the mortality from EAA increased marginally from 0.04 (95% CI 0.03-0.05) in the 1968-1972 calendar period to 0.08 (95% CI 0.07-0.09) in the 2005-2008 period. Mortality from Sarcoidosis increased by approximately 9% a year.
Discussion: Our findings show that the mortality from Asbestosis continues to rise in the UK. Overall mortality rates from EAA remained stable throughout the same period but it was higher in males and in older people. There was a slight increase in mortality from Sarcoidosis over the study period which was greater in women.

Kukkonen, M.K. e.a. (2011)

Kukkonen, M.K. e.a. (2011). Genetic susceptibility to asbestos-related fibrotic pleuropulmonary changes. Eur Respir J. 2011 Sep;38(3):672-8.
Abstract
The objective of this study was to determine whether genetic polymorphisms in enzymes that metabolise oxidative agents modify the individual susceptibility to developing asbestos and smoking-related pleuropulmonary changes. Nine polymorphisms of six genes (EPHX1, GSTM1, GSTM3, GSTP1, GSTT1 and NAT2) were genotyped from 1,008 Finnish asbestos-exposed workers. The genotype data were compared to signs of lung fibrosis and pleural thickenings, as well as with total lung capacity, single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) and specific diffusing capacity (expressed as D(L,CO) per unit of alveolar volume (V(A))). The GSTT1 deletion polymorphism was associated with fibrotic changes (p=0.003), and decreased D(L,CO) (p=0.02) and D(L,CO)/V(A) (p=0.002), and the GSTM1 deletion polymorphism was associated with the greatest thickness of pleural plaques (p=0.009). On further analysis, the GSTT1 null genotype was found to pose over a three-fold risk for severe fibrotic changes (OR 3.12, 95% CI 1.51-6.43), and around two-fold risks for decreased D(L,CO) (OR 1.77, 95% CI 1.06-2.95) and D(L,CO)/V(A) (OR 2.37, 95% CI 1.33-4.23). In addition, the GSTM1 null genotype showed an elevated risk (OR 1.36, 95% CI 1.03-1.80) for thicker pleural plaques. Our data suggest that inherited detoxification capacity may affect the development and severity of asbestos and smoking-related nonmalignant pulmonary changes

Lenters, V. e.a. (2011)

Lenters, V. e.a. (2011). A Meta-Analysis of Asbestos and Lung Cancer: Is Better Quality Exposure Assessment Associated with Steeper Slopes of the Exposure-Response Relationships? Environ Health Perspect. 2011 Jun 27.
Abstract
Objective:
Asbestos is a well recognized cause of lung cancer but there is considerable heterogeneity between studies in the slope of exposure-response relationship. We considered the role of quality of the exposure assessment to potentially explain heterogeneity in exposure-response slope estimates.
Data Sources: We searched MEDLINE (1950-2009) for studies with quantitative estimates of cumulative asbestos exposure and lung cancer mortality, and identified 19 original epidemiological studies. One was a population-based case-control study and others were industry-based cohort studies. Data Extraction: Cumulative exposure categories and corresponding risks were abstracted. Exposure-response slopes (KL) were calculated using linear relative risk regression models.
Data Synthesis: Quality assessment of five exposure assessment aspects of each study was performed, and random effects univariate and multivariate meta-regressions were conducted. Heterogeneity in exposure-response relationships was greater than expected by chance (I2=64%). Stratification by exposure assessment characteristics revealed that studies with well-documented exposure assessment, larger contrast in exposure, greater coverage of the exposure history by exposure measurement data, and more complete job histories, had higher meta-KL values than studies without these characteristics. The latter two covariates were most strongly associated with the KL value. Meta-KL values increased when analyses were incrementally restricted to higher quality studies.
Conclusions: This meta-analysis indicates that studies with higher quality asbestos exposure assessment yield higher meta-estimates of the lung cancer risk per unit of exposure. Potency differences for predominantly chrysotile versus amphibole asbestos exposed cohorts become difficult to ascertain, when meta-analyses are restricted to studies with fewer exposure assessment limitations.

Ameille, J. e.a. (2011)

Ameille, J. e.a. (2011). Asbestos-Related Diseases in Automobile Mechanics. Ann Occup Hyg. 2011 Sep 28
Abstract
Purpose
Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyse the frequency of pleural and parenchymal abnormalities on high-resolution computed tomography (HRCT) in a population of automobile mechanics.
Methods
The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos-related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers; who in the case of disagreement discussed until they reached agreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques.
Results
Pleural plaques were observed in five cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in one case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques.
Conclusions
The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers.

Camargo M.C. e.a. (2011)

Camargo M.C. e.a. (2011). Occupational exposure to asbestos and ovarian cancer: a meta-analysis. Environ Health Perspect. 2011 Sep;119(9):1211-7.
Abstract
Objective:
A recent Monographs Working Group of the International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence for a causal association between exposure to asbestos and ovarian cancer. We performed a meta-analysis to quantitatively evaluate this association.
Data sources: Searches of PubMed and unpublished data yielded a total of 18 cohort studies of women occupationally exposed to asbestos.
Data extraction: Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer.
Data synthesis: All but one study reported standardized mortality ratios (SMRs) comparing observed numbers of deaths with expected numbers for the general population; the exception was a study that reported standardized incidence ratios. For simplicity, we refer to all effect estimates as SMRs. The overall pooled SMR estimate for ovarian cancer was 1.77 (95% confidence interval, 1.37-2.28), with a moderate degree of heterogeneity among the studies (I2 = 35.3%, p = 0.061). Effect estimates were stronger for cohorts compensated for asbestosis, cohorts with estimated lung cancer SMRs > 2.0, and studies conducted in Europe compared with other geographic regions. Effect estimates were similar for studies with and without pathologic confirmation, and we found no evidence of publication bias (Egger's test p-value = 0.162). Conclusions: Our study supports the IARC conclusion that exposure to asbestos is associated with increased risk of ovarian cancer.

Lacourt A., e.a. (2011)

Lacourt A., e.a. (2011). Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma.Eur Respir J. 2011 Nov 10.
Abstract
Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM, using case-control data in males.Cases were selected from a French case-control study conducted in 1987-1993 and the French National Mesothelioma Surveillance Program in 1998-2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose-response relationships were estimated using restricted cubic spline functions in logistic regression models.A total of 2,466 ever asbestos exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 years and continued to increase until 30 years after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased.These results based on a large population-based case-control study underline the need to take into account the temporal pattern of exposure on risk assessment.

Damhuis, R.A. e.a. (2011)

Damhuis, R.A. e.a. (2011). Population-based survival for malignant mesothelioma after introduction of novel chemotherapy. Eur Respir J. 2011 Dec 1.
Abstract
Malignant mesothelioma is known for its dismal prognosis and poor response to conventional treatment. Chemotherapy with cisplatin-antifolate combinations recently showed promising response rates and prolonged survival in randomised trials.To assess the impact of this development on clinical practice and survival at a population-based level, treatment patterns and survival trends were studied for patients diagnosed with mesothelioma in the period 1995-2006. 4731 records were retrieved from the Netherlands Cancer Registry and chemotherapy use and median survival were analysed.For the periods 1995-1998 to 2005-2006, chemotherapy use increased from 8% to 36%. Median survival increased over time from 7.1 months to 9.2 months. For pleural mesothelioma, multivariable analysis demonstrated that survival was poorer for elderly patients and sarcomatoid tumours. The prognostic impact of chemotherapy increased with time. Median survival for chemotherapy treated patients improved from 10.1 months (1995-1998) to 13.1 months (2005-2006). For peritoneal mesothelioma, median survival was poor (3.9 months) but better for females and younger patients.This study demonstrates that chemotherapy use increased at a national level and coincided with an improvement in survival. The novel chemotherapy regimen appears to be more effective but, due to the observational nature of this study, alternative explanations cannot be excluded.

Musk, A.W. e.a. (2011)

Musk, A.W. e.a. (2011). Predicting survival in malignant mesothelioma. Eur Respir J. 2011 Dec;38(6):1420-4.
Abstract
Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs. Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis. Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2-1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1-1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0-198), 177 (48-350), 221 (97-504), 238 (108-502) and 301 (134-611) days; ∼4 weeks of this apparent improvement can be attributed to earlier diagnosis. With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.

Fazzo, L. e.a. (2011)

Fazzo, L. e.a. (2011). Pleural mesothelioma mortality and asbestos exposure mapping in Italy. Am J Ind Med. 2012 Jan;55(1):11-24. doi: 10.1002/ajim.21015.
Abstract
Background:
An epidemic of asbestos-related diseases is ongoing worldwide. Mortality from malignant pleural neoplasms in Italy was analyzed, to estimate the health impact of asbestos at national and local level.
Methods: Mortality from ICD-9 code 163 was considered, in the time-window 1995-2002, using National Bureau of Statistics data. National and regional standardized rates and municipal Standardized Mortality Ratios (SMR) were calculated. Municipal clusters were identified by applying Spatial Scan Statistics procedure. Relative risks (RR) express the ratio of risk within the cluster to the risk outside the cluster.
Results: The national standardized annual mortality rate was 1.9 per 100,000. Significant clusters corresponded to asbestos-cement industries (Casale Monferrato: RR = 11.63), shipyards (Monfalcone, RR = 7.43), oil refineries (Falconara, RR = 2.52), petrochemical industries (Priolo, RR = 3.81).
Conclusions: The present study confirms malignant pleural neoplasms mortality as a suitable indicator of asbestos exposure at geographic level. In addition to asbestos-cement industries and shipyards, other industrial settings are associated with pleural neoplasm mortality.

Menegozzo, S. e.a. (2011)

Menegozzo, S. e.a. (2011). Mortality study in an asbestos cement factory in Naples, Italy.Ann Ist Super Sanita. 2011;47(3):296-304.
Abstract
The objective of this paper is to investigate mortality among 1247 male asbestos-cement workers employed in an asbestos-cement plant located in Naples. The cohort included 1247 men hired between 1950 and 1986. The follow-up began on January 1st 1965. The vital status and causes of death were ascertained up to December 31 2005. Cause-specific mortality rates of the Campania Region population were used as reference. Relative risks were estimated using Standardized Mortality Ratios (SMRs), and the confidence intervals were calculated at a 95% level (95% CI). A significant increase in mortality was observed for respiratory disease (81 deaths; SMR = 187; 95% CI = 149- 233), particularly for pneumoconiosis (42 deaths; SMR = 13 313; 95% CI = 9595-17 996) of which 41 deaths for asbestosis (SMR = 43 385; 95% CI = 31 134-58 857), for pleural cancer (24 deaths; SMR = 2617; 95% CI = 1677-3893), for lung cancer (84 deaths; SMR=153; 95% CI = 122-189) and for peritoneal cancer (9 deaths; SMR = 1985; 95% CI = 908-3769). Non-significant increases were also observed for rectum cancer (6 deaths; SMR = 157; 95% CI = 58-342). In conclusion, consistently with other mortality studies on asbestos-cement workers performed in different countries, an increased mortality from asbestosis, lung cancer, pleural and peritoneal mesothelioma was detected in the present cohort.

Prieto, M.A. e.a. (2011)

Prieto, M.A. e.a. (2011). Opinions and expectations of patients with health problems associated to asbestos exposure. An Sist Sanit Navar. 2011 Jan-Apr;34(1):33-42.
Abstract
Background:
The prevalence of diseases related to asbestos exposure requires the development of monitoring programs and specific health care protocols. The aim of this study is to determine the opinions and expectations of former workers of an asbestos factory, in order to adapt the care process to the needs of the affected population, and to learn about the activity of the association that represents them.
Methods: Qualitative study. Focus groups with former employees of a corrugated asbestos factory, members of the association AVIDA (Seville). Recording and transcription of interviews. Discourse analysis with Nudist Vivo 1.0.
Results: All respondents have health problems, including asbestosis, lung cancer and mesothelioma. Through the association, they are involved in an ongoing process of negotiation with the public administration, to improve healthcare, achieve recognition as having an occupational disease and the payment of compensation. The lack of monitoring and continuity in care is designated as the major problem in the current care process. They welcome the creation of special care units, the good treatment received and the quality of technical instruments in the public health system. On the contrary, they criticize the difficulties in finding an accurate diagnosis, the lack of continuity of care, and the bureaucratic difficulties and lack of specific care directed to affected relatives. The participants' expectations highlight their intention to participate in the development of future programs and protocols.
Conclusions: This study confirms the multifactor nature of diseases related to asbestos exposure and the importance of determining the needs and demands of the affected population in order to improve health care.

Dragonieri S. e.a. (2011)

Dragonieri S e.a. (2011). An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls. Lung Cancer. 2011 Sep 14.
Abstract
Background:
Malignant Pleural Mesothelioma (MPM) is a tumour of the surface cells of the pleura that is highly aggressive and mainly caused by asbestos exposure. Electronic noses capture the spectrum of exhaled volatile organic compounds (VOCs) providing a composite biomarker profile (breathprint).
Objective: We tested the hypothesis that an electronic nose can discriminate exhaled air of patients with MPM from subjects with a similar long-term professional exposure to asbestos without MPM and from healthy controls.
Methods: 13 patients with a histology confirmed diagnosis of MPM (age 60.9±12.2 year), 13 subjects with certified, long-term professional asbestos exposure (age 67.2±9.8), and 13 healthy subjects without asbestos exposure (age 52.2±16.2) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by an electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validated accuracy (CVA) was calculated.
Results: Breathprints from patients with MPM were separated from subjects with asbestos exposure (CVA: 80.8%, sensitivity 92.3%, specificity 85.7%). MPM was also distinguished from healthy controls (CVA: 84.6%). Repeated measurements confirmed these results.
Conclusions: Molecular pattern recognition of exhaled breath can correctly distinguish patients with MPM from subjects with similar occupational asbestos exposure without MPM and from healthy controls. This suggests that breathprints obtained by electronic nose have diagnostic potential for MPM.

Schuhmann, M. e.a. (2011)

Schuhmann, M. e.a. (2011). Asbestos-related Lung Disease: An Update. Clinical Pulmonary Medicine: November 2011 - Volume 18 - Issue 6 - p 265–273.
Abstract
In this work, we describe both benign and malignant asbestos-related diseases and provide an updated review of recent advances in the field. It has long been appreciated that the inhalation of asbestos fibers causes several well-described respiratory diseases including pleural plaques, diffuse pleural thickening, asbestosis, lung cancer, and malignant pleural mesothelioma (MPM). However, despite this knowledge and stricter industrial controls, the incidence of these diseases continues to increase in many parts of the world. In fact, despite the introduction of strict limits early in the 20th century, the mortality rate due to MPM is still increasing in industrialized countries such as the United Kingdom and Australia. In this update we provide an overview of each disease entity while concentrating on the role that newer imaging techniques, including high-resolution computed tomography, magnetic resonance imaging, and positron emission tomography /computed tomography, play in the diagnosis of asbestos-related pleural and parenchymal diseases. As the incidence of MPM continues to increase in many parts of the world, this review also focuses on new approaches to the diagnosis and treatment of this devastating condition. A description of the potential use and limitations of biomarkers in the diagnosis and monitoring of the disease is included along with recent trial data examining novel vaccine-based biological therapies.

Baur, X. e.a. (2011)

Baur, X. e.a. (2011). Diagnosing and expertizing asbestos-induced occupational diseases. Dtsch Med Wochenschr. 2011 Nov;136(45):2319-24.
Abstract
Due to latency periods that can last for decades, asbestos-related diseases show 18 years after the enforcement of the prohibition of asbestos application in Germany their highest numbers. In the centre of attention are asbestos-induced pleural fibroses, mesotheliomas, asbestoses, lung and laryngeal cancer. Diagnosing and expertizing these diseases causes difficulties, is hitherto non-uniform and does frequently not correspond to the current medico-scientific expertise. This induced the German Respiratory Society as well as the German Society of Occupational and Environmental Medicine in cooperation with the German Society of Pathology, the German Radiology Society and the German Society of Otorhinolaryngology, Head and Cervical Surgery, to develop the above mentioned guideline during seven meetings moderated by AWMF. The required thorough diagnosis is based on the detailed recording of a qualified occupational history. Since the sole radiological and pathological-anatomical findings cannot sufficiently contribute to the causal relationship the occupational history recorded by a general physician and a specialist is of decisive importance. These physicians have to report suspected occupational diseases and to advise patients on social and medical questions. Frequently, problems occur if the recognition of an occupational disease is neglected due to a supposedly too low exposure or too few ferruginous bodies or low fibre concentrations in lung tissue. The new S2k directive summarizing the current medico-scientific knowledge is for this reason, for diagnoses and expert opinions as well as for the determination of a reduced capacity for work a very important source of information.

Chen, M. e.a. (2011)

Chen, M. e.a. (2011). Mesothelioma and lung cancer mortality: A historical cohort study among asbestosis workers in Hong Kong. Lung Cancer. 2011 Nov 28.
Abstract
Objectives
: To investigate the mortality pattern among a cohort of workers with asbestosis in Hong Kong, with special emphases on mesothelioma and lung cancer.
Methods: All 124 male workers with confirmed asbestosis in Hong Kong during 1981-2008 were followed up to December 31, 2008 to ascertain the vital status and causes of death. Standardized mortality ratio (SMR) for each underlying cause of death was calculated by using person-year method. Axelson's indirect method was applied to adjust for the potential confounding effect of cigarette smoking.
Results: A total of 86 deaths were observed after 432.8 person-years of observations. The SMR for overall mortality (6.06, 95% CI: 4.90-7.51) increased significantly. The elevated risk of deaths from all cancers (7.53, 95% CI: 5.38-10.25) was mainly resulted from a significantly excess risk from lung cancer (SMR=7.91, 95% CI: 4.32-13.29, 14 deaths) and mesothelioma (SMR=6013.63, 95% CI: 3505.95-9621.81, 17 deaths). The SMR for lung cancer retained statistically significant after adjustment of smoking. An increased smoking adjusted SMR was also suggested for all heart diseases (2.32, 95% CI: 0.93-4.79, 7 deaths) and acute myocardial infarction (3.10, 95% CI: 0.84-7.94, 4 deaths), though the statistical significance was borderline. We found a positive association with net years of exposure to asbestos for mesothelioma and lung cancer. Conclusions: Our study provided further evidence on the carcinogenesis of asbestos/asbestosis with the risk of deaths from lung cancer and mesothelioma. This study also provided a preliminary support for a possible link between asbestosis and heart disease, but power is limited.

Kumagai-Takei, N. e.a. (2011)

Kumagai-Takei, N. e.a. (2011). Asbestos induces reduction of tumor immunity.Clin Dev Immunol. 2011;2011:481439.
Abstract
Asbestos-related cancers such as malignant mesothelioma and lung cancer are an important issue in the world. There are many conflicts concerning economical considerations and medical evidence for these cancers and much confusion regarding details of the pathological mechanisms of asbestos-induced cancers. For example, there is uncertainty concerning the degree of danger of the iron-absent chrysotile compared with iron-containing crocidolite and amosite. However, regarding bad prognosis of mesothelioma, medical approaches to ensure the recognition of the biological effects of asbestos and the pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect the early stage of mesothelioma, should result in better preventions and the cure of these malignancies. We have been investigating the immunological effects of asbestos in relation to the reduction of tumor immunity. In this paper, cellular and molecular approaches to clarify the immunological effects of asbestos are described, and all the findings indicate that the reduction of tumor immunity is caused by asbestos exposure and involvement in asbestos-induced cancers. These investigations may not only allow the clear recognition of the biological effects of asbestos, but also present a novel procedure for early detection of previous asbestos exposure and the presence of mesothelioma as well as the chemoprevention of asbestos-related cancers.

Elliott, L. e.a. (2012)

Elliott, L. e.a. (2012). Lung cancer mortality in North Carolina and South Carolina chrysotile asbestos textile workers. OEM Online First, published on January 20, 2012 as 10.1136/oemed-2011-100229. 
Abstract
Objectives
Studies of workers in two US cohorts of asbestos textile workers exposed to chrysotile (North Carolina (NC) and South Carolina (SC)) found increasing risk of lung cancer mortality with cumulative fibre exposure. However, the risk appeared to increase more steeply in SC, possibly due to differences in study methods. The authors conducted pooled analyses of the cohorts and investigated the exposure-disease relationship using uniform cohort inclusion criteria and statistical methods.
Methods
Workers were included after 30 days of employment in a production job during qualifying years, and vital status ascertained through 2003 (2001 for SC). Poisson regression was used to estimate the exposure-response relationship between asbestos and lung cancer, using both exponential and linear relative rate models adjusted for age, sex, race, birth cohort and decade of follow-up.
Results
The cohort included 6136 workers, contributing 218 631 person-years of observation and 3356 deaths. Cumulative exposures at the four study facilities varied considerably. The pooled relative rate for lung cancer, comparing 100 f-yr/ml to 0 f-yr/ml, was 1.11 (95% CI 1.06 to 1.16) for the combined cohort, with different effects in the NC cohort (RR=1.10, 95% CI 1.03 to 1.16) and the SC cohort (RR=1.67, 95% CI 1.44 to 1.93).
Conclusions
Increased rates of lung cancer were significantly associated with cumulative fibre exposure overall and in both the Carolina asbestos-textile cohorts. Previously reported differences in exposure-response between the cohorts do not appear to be related to inclusion criteria or analytical methods.

Robinson, C. e.a. (2012)

Robinson, C. e.a. (2012). The Antioxidants Vitamins A and E and Selenium Do Not Reduce the Incidence of Asbestos-Induced Disease in a Mouse Model of Mesothelioma, Nutrition and Cancer, 64:2, 315-322.
Abstract
Epidemiological evidence indicates that supplementation with some dietary factors is associated with a lower incidence of cancer. An effective cancer prevention strategy for the millions of people worldwidewho have been exposed to asbestos could have enormous benefit.We tested whether dietary supplementation of the antioxidants vitamin A, E, and selenium could alter the pattern of disease in the MexTAg transgenic mouse model, in which mice uniformly develop mesothelioma after asbestos exposure. We focused on antioxidants because one of the most widely accepted hypotheses for the mechanism by which asbestos fibers cause cancer proposes the involvement of reactive oxygen and nitrogen species.We compared the survival ofMexTAgmice that had been inoculated with asbestos fed on diets supplemented with 250,000 IU/kg vitamin A (retinoic acid), or 1,000 mg/kg vitamin E (α-tocopherol acetate) or 3 mg/kg selenium, or both vitamin E and selenium concurrently and, additionally, diets deficient in each antioxidant. We found that neither the time to develop symptoms of disease nor overall survival times were altered by any of the diets. We conclude that the data do not support the notion that dietary antioxidants will moderate the rate of mesothelioma in asbestos-exposed populations.

Dumortier, P. & Vuyst, P. de (2012)

Dumortier, P. & Vuyst, P. de (2012). Asbestos Exposure During Uncontrolled Removal of Sprayed-on Asbestos. Ann. Occup. Hyg., Vol. 56, No. 1, pp. 49–54, 2012.
Asbestos-containing materials in place in buildings, especially sprayed-on asbestos, are still an important health threat. Clearance of these materials has to be operated by specifically trained workers wearing specific individual protection suits after containment of the contaminated area. Good work practices are, however, not always applied.We report the case of two workers hired for 1 week to remove sprayed-on amosite asbestos during the remodeling of a former industrial hall. Regulatory protective equipments were not used. A legal action was initiated after disclosure of the working conditions. Medical examinations were performed 18 and 22 months after exposure. Workers denied any other asbestos exposure. Lung function tests and chest computed tomography scans were normal. Very high levels of asbestos fibers and bodies were discovered on mineralogical analysis of bronchoalveolar lavage fluid (BALF) by phase contrast light microscopy and analytical electron microscopy. All fibers were amosite. An extrapolation considering duration of exposure, breathing pattern, and BALF fiber content suggests that the workers were exposed to airborne fiber concentrations in the range from several tens to about a hundred World Health Organization fibers per milliliter air. In conclusion, exposures to historical airborne fiber levels prevailing half a century ago may still occur today when the work regulations are not applied. In these conditions, even very short exposures may result in considerable lung fiber retention in case of amphibole exposure with the subsequent risk for developing asbestos-related diseases. Fiber analysis in BALF is useful to clarify such exposures.

Phelka, A.D. & Finley, B.L. (2012)

Phelka, A.D. & Finley, B.L. (2012). Potential health hazards associated with exposures to asbestos-containing drywall accessory products: A state-of-the-science assessment. Critical Reviews in Toxicology, 2012; 42(1): 1–27.
Abstract
Until the late 1970s, chrysotile asbestos was an ingredient in most industrial and consumer drywall accessory products manufactured in the US. In 1977, the Consumer Product Safety Commission (CPSC) issued a ban of consumer patching compounds containing “respirable, free-form asbestos” based on their prediction of exceptionally high rates of asbestos-related diseases among individuals using patching compounds for as little as a few days. Although hundreds of thousands of workers and homeowners handling these products may have experienced exposure to asbestos prior to the ban, there has been no systematic effort to summarize and interpret the information relevant to the potential health effects of such exposures. In this analysis, we provide a comprehensive review and analysis of the scientific studies assessing fiber type and dimension, toxicological and epidemiological endpoints, and airborne fiber concentrations associated with joint compound use. We conclude that: 1) asbestos in drywall accessory products was primarily short fiber (< 5 μm) chrysotile, 2) asbestos in inhaled joint compound particulate is probably not biopersistent in the lung, 3) estimated cumulative chrysotile exposures experienced by workers and homeowners are below levels known to be associated with respiratory disease, and 4) mortality studies of drywall installers have not demonstrated a significantly increased incidence of death attributable to any asbestos-related disease. Consequently, contrary to the predictions of the CPSC, the current weight of evidence does not indicate any clear health risks associated with the use of asbestos-containing drywall accessory products. We also describe information gaps and suggest possible areas of future research.

La Vecchia & Bofetta (2012)

La Vecchia & Bofetta (2012). Role of stopping exposure and recent exposure to asbestos in the risk of mesothelioma. Eur J Cancer Prev. 2012 Feb 5.
The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure, if any, is, however, open to discussion. A literature review was conducted to the end of 2010. In a cohort of 1966 Italian textile workers, the standardized mortality ratio, on the basis of 68 deaths from mesothelioma, was 6627 for workers employed only under the age of 30 years, 8019 for those employed both under the age of 30 years and at the age of 30–39 years, and 5891 for those employed both under the age of 30 years and at the age of 40 years or more. In a cohort of Italian asbestos cement workers, including 135 deaths from pleural cancer, compared with workers who had stopped exposure for 3–15 years, the relative risk (RR) was similar for those still employed (RR =0.67) and for those who had stopped for 30 years or more (RR= 0.65). In a British case–control study, including 622 cases of mesothelioma and 1420 population controls, the RR substantially increased with increasing duration of exposure under the age of 30 years, but not with exposure at the age of more than 30 years. In the Great Britain Asbestos Workers Survey, including 649 deaths from mesothelioma compared with workers who were still employed and or had stopped for less than 10 years, the multivariate RRs were 0.90 10–20 years after stopping exposure and 0.99 both 20–30 and more than 30 years after stopping. There is consistent evidence showing that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures, and that stopping exposure does not materially modify the subsequent risk of mesothelioma.

Mc Cormack, V. e.a. (2012)

Mc Cormack, V. e.a. (2012). Estimating the asbestos-related lung cancer burden from mesothelioma mortality. British Journal of Cancer (2012), 1 –10.
Background:
Quantifying the asbestos-related lung cancer burden is difficult in the presence of this disease’s multiple causes. We explore two methods to estimate this burden using mesothelioma deaths as a proxy for asbestos exposure.
Methods: From the follow-up of 55 asbestos cohorts, we estimated ratios of (i) absolute number of asbestos-related lung cancers to mesothelioma deaths; (ii) excess lung cancer relative risk (%) to mesothelioma mortality per 1000 non-asbestos-related deaths.
Results: Ratios varied by asbestos type; there were a mean 0.7 (95% confidence interval 0.5, 1.0) asbestos-related lung cancers per mesothelioma death in crocidolite cohorts (n¼6 estimates), 6.1 (3.6, 10.5) in chrysotile (n¼16), 4.0 (2.8, 5.9) in amosite (n¼4) and 1.9 (1.4, 2.6) in mixed asbestos fibre cohorts (n¼31). In a population with 2 mesothelioma deaths per 1000 deaths at ages 40–84 years (e.g., US men), the estimated lung cancer population attributable fraction due to mixed asbestos was estimated to be 4.0%.
Conclusion: All types of asbestos fibres kill at least twice as many people through lung cancer than through mesothelioma, except for crocidolite. For chrysotile, widely consumed today, asbestos-related lung cancers cannot be robustly estimated from few mesothelioma deaths and the latter cannot be used to infer no excess risk of lung or other cancers.

Barbieri, P.G. e.a. (2012)

Barbieri, P.G. e.a. (2012). Asbestos Fibre Burden in the Lungs of Patients with Mesothelioma Who Lived Near Asbestos-Cement Factories. Ann Occup Hyg. 2012 Jan 12.
Abstract
Background

Epidemics of malignant mesothelioma are occurring among inhabitants of Casale Monferrato and Bari never employed in the local asbestos-cement (AC) factories. The mesothelioma risk increased with proximity of residence to both plants.ObjectivesTo provide information on the intensity of environmental asbestos exposure, in the general population living around these factories, through the evaluation of the lung fibre burden in mesothelioma patients.MethodsWe analysed by a scanning electron microscope equipped with X-ray microanalysis wet (formalin-fixed) lung tissue samples from eight mesothelioma patients who lived in Casale Monferrato or Bari and underwent surgery. Their occupational and residential history was obtained during face-to-face interviews. Semi-quantitative and quantitative indices of cumulative environmental exposure to asbestos were computed, based on residential distance from the AC plants and duration of stay.ResultsThe lung fibre burden ranged from 110 000 to 4 300 000 fibres per gram of dry lung (f/g) and was >1 000 000 f/g in three subjects. In four cases, only amphibole fibres were detected. Environmental exposures had ceased at least 10 years before samples were taken. No patient had other definite or probable asbestos exposures. A linear relationship was observed between the lung fibre burden and all three indices of environmental cumulative exposure to asbestos.ConclusionsEnvironmental exposure to a mixture of asbestos fibres may lead to a high lung fibre burden of amphiboles years after exposure cessation. The epidemiological evidence of an increased mesothelioma risk for the general population of Casale Monferrato and Bari, associated with asbestos contamination of the living environment, is corroborated.

Metintas, S. e.a. (2012)

Metintas, S. e.a. (2012). Environmental asbestos exposure in rural Turkey and risk of lung cancer. International Journal of Environmental Health Research 2012, 1-12, i First article.
Abstract
The aim of this study was to determine the risk of lung cancer in a cohort of villagers with environmental asbestos exposure. The study was carried out as a field-based epidemiological study. Information from 3143 individuals in 15 asbestos exposed villages and 2175 individuals in 12 control villages was obtained. Asbestos fiber type to which villagers were exposed mainly was tremolite or tremolite, actinolite, chrysotile mixtures. The cumulative fiber count of the villagers during their lifespan ranged from 0.19 to 4.61 fiber-years/ml. The annual average incidence ratio of lung cancer was 135.21/100,000 persons/year in men and 47.28 in women in the asbestos exposed villages. For the control villages, this ratio was 60.15/100,000 person/year in men and 15.06 in women. Being a male, advanced age, smoking and asbestos exposure were established to increase the risk of lung cancer. Environmental asbestos exposure in rural area is a risk factor for lung cancer independent of smoking.

Riaz, S.P. e.a. (2012)

Riaz, S.P. e.a. (2012). Mesothelioma incidence projections in South East England. Eur Respir J. 2012 Jan 26.
Abstract
We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England.We extracted data on patients diagnosed with mesothelioma (ICD-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods.A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter.The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and due to the long latency period the incidence of mesothelioma is projected to increase until the 2020s.

Marinaccio, A. e.a. (2012)

Marinaccio, A. e.a. (2012). Mesothelioma incidence surveillance systems and claims for workers' compensation. Epidemiological evidence and prospects for an integrated framework.BMC Public Health. 2012 Apr 30;12(1):314.
ABSTRACT:
BACKGROUND:
Malignant mesothelioma is an aggressive and lethal tumour strongly associated with exposure to asbestos (mainly occupational). In Italy a large part of workers are protected from professional diseases by public insurance and it is active an epidemiological surveillance system for incident mesothelioma cases.
METHODS: We set up an individual linkage between the Italian national mesothelioma register (ReNaM) and the Italian workers' compensation authority (INAIL) archives. Logistic regression models were used to identify and test explanatory variables.
RESULTS: We extracted 3270 mesothelioma cases with occupational origins from the ReNaM, matching them with 1625 subjects in INAIL (49.7%); 91.2% (1,482) of the claims received compensation. The risk of not seeking compensation is significantly higher for women and old people. Claims have increased significantly in recent years and there is a clear geographical gradient (northern and more developed regions having higher claims rates). The highest rates of compensation claims were after work known to involve asbestos.
CONCLUSIONS: Our data illustrate the importance of documentation and dissemination of all asbestos exposure modalities. Strategies focused on structural and systematic interaction between epidemiological surveillance and insurance systems are needed.

Valk, F.M. van der & Leeuwen, J. van (2012)

Valk, F.M. van der & Leeuwen, J. van (2012). Maligne peritoneaal mesothelioom, een moeilijk te stellen diagnose. Ned Tijdschr Geneeskd. 2012;156:A4269.
Achtergrond
Het maligne mesothelioom is een agressief neoplasma, dat uitgaat van sereuze membranen, zoals de pleura en het peritoneum. Een maligne peritoneaal mesothelioom is relatief zeldzaam, maar de incidentie stijgt wereldwijd door intensief asbestgebruik tijdens de 20e eeuw.
Casus
Een 60-jarige man had last van algehele malaise, nachtzweten en gewichtsverlies en werd door de internist onderzocht. Aanvullend onderzoek bestond onder meer uit een CT-scan, 2 PET-CT-scans, 2 diagnostische laparoscopieën en histologisch onderzoek van peritoneumbiopten. Na 7 maanden werd de diagnosis ‘maligne peritoneaal mesothelioom’ gesteld.
Conclusie
Bij aanwijzingen voor een maligne peritoneaal mesothelioom is histologisch onderzoek van groot belang. Consensus over de optimale behandeling is er nog niet, maar een klein overlevingsvoordeel is te behalen met systemische chemotherapie of intraperitoneale therapie bestaande uit hyperthermische intraperitoneale chemotherapie na cytoreductieve chirurgie.

Harding, A.H. e.a. (2012)

Harding, A.H. e.a. (2012). Cardiovascular disease mortality among British asbestos workers (1971-2005).Occup Environ Med. 2012 Jun;69(6):417-21.
Abstract
Objectives Asbestos is an inflammatory agent, and there is evidence that inflammatory processes are involved in the development of cardiovascular disease. Whether asbestos is a risk factor for cardiovascular disease has not been established. The objective of this study was to investigate cardiovascular disease mortality in a large cohort of workers occupationally exposed to asbestos. Methods Cardiovascular disease mortality in a cohort of 98 912 asbestos workers, with median follow-up of 19 years, was analysed. Unadjusted and smoking-adjusted standardised mortality ratios (SMRs) were calculated. The association between indicators of asbestos exposure and mortality was analysed with Poisson regression models, for deaths occurring during the period 1971-2005. Results Altogether 15 557 deaths from all causes, 1053 deaths from cerebrovascular disease and 4185 deaths from ischaemic heart disease (IHD) occurred during follow-up. There was statistically significant excess mortality from cerebrovascular disease (SMR: men 1.63, women 2.04) and IHD (SMR: men 1.39, women 1.89). Job and birth cohort were associated with the risk of cerebrovascular and IHD mortality in the Poisson regression model including sex, age, smoking status, job, cohort and duration of exposure. For IHD only, duration of exposure was also statistically significant in this model. Conclusions Cerebrovascular and IHD mortality was significantly higher among these asbestos workers than in the general population and within the cohort mortality was associated with indicators of asbestos exposure. These findings provide some evidence that occupational exposure to asbestos was associated with cardiovascular disease mortality in this group of workers.

Bij, S. van der e.a. (2012)

Bij, S. van der e.a. (2012). Prognosis and prognostic factors of patients with mesothelioma: a population-based study. Br J Cancer. 2012 May 29. doi: 10.1038/bjc.2012.245.
Abstract
Background:
It is important to regularly update survival estimates of patients with malignant mesothelioma as prognosis may vary according to epidemiologic factors and diagnostic and therapeutic management.
Methods: We assessed overall (baseline) survival as well as related prognostic variables in a large cohort of 1353 patients with a confirmed diagnosis of malignant mesothelioma between 2005 and 2008.
Results: About 50% of the patients were 70 years or older at diagnosis and the median latency time since start of asbestos exposure was 49 years. One year after diagnosis, 47% of the patients were alive, 20% after 2 years and 15% after 3 years. Prognostic variables independently associated with worse survival were: older age (HR=1.04 per year 95% CI (1.03-1.06)), sarcomatoid subtype (HR=2.45 95% CI (2.06-2.90)) and non-pleural localisation (HR=1.67 95% CI (1.26-2.22)).
Conclusion: Survival of patients with malignant mesothelioma is still limited and depends highly on patient age, mesothelioma subtype and localisation. In addition, a substantial part of the patients had a long latency time between asbestos exposure and diagnosis.

Siesling, S. e.a. (2012)

Siesling, S. e.a. (2012). Rare thoracic cancers, including peritoneum mesothelioma. Eur J Cancer. 2012 May;48(7):949-60.
Abstract

Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) and followed-up to 31st December 2003. Over 17,688 cases of rare thoracic cancers were selected based on the list of the RACECARE project. Mesothelioma was the most common tumour (19 per million per year) followed by epithelial tumours of the trachea and thymus (1.3 and 1.7, respectively). The age standardised incidence rates of epithelial tumours of the trachea was double in Eastern and Southern Europe versus the other European regions: 2 per million per year. Epithelial tumours of the thymus had the lowest incidence in Northern and Eastern Europe and UK and Ireland(1) and somewhat higher incidence in Central and Southern Europe.(2) Highest incidence in mesothelioma was seen in UK and Ireland(23) and lowest in Eastern Europe.(4) Patients with tumours of the thymus had the best prognosis (1-year survival 85%, 66% at 5 years). Five year survival was lowest for the mesothelioma 5% compared to 14% of patients with tumours of the trachea. Mesothelioma was the most prevalent rare cancer (12,000 cases), followed by thymus (7000) and trachea (1400). Cancer Registry (CR) data play an important role in revealing the burden of rare thoracic cancers and monitoring the effect of regulations on asbestos use and smoking related policies.

Jasani, B & Gibbs, A. (2012)

Jasani, B & Gibbs, A. (2012). Mesothelioma not associated with asbestos exposure. Arch Pathol Lab Med. 2012 Mar;136(3):262-7. 
Abstract
Context
: Despite asbestos being identified as the single most important cause of malignant mesothelioma, the tumor is known to occur in only 10% to 20% of heavily exposed individuals. In addition, about 20% of the patients have no history of asbestos exposure even after detailed assessment. Therefore, there has been speculation for some time that asbestos alone may not be sufficient to cause mesothelioma and that other factors may be involved either as cocarcinogens or as independent mechanisms of cancer causation.
Objective: To give a brief review of nonasbestos fiber erionite and therapeutic radiation as 2 established examples of asbestos-independent mechanisms, of the potential emerging role of man-made fibers such as carbon nanotubes, and of polyoma virus SV40 (simian virus 40) as a potential example of the cocarcinogenic mode of involvement.
Data sources: Relevant recent literature has been surveyed to portray and provide the evidence in favor of the examples.
Conclusions: Erionite has emerged as the most important example of nonasbestos-mediated cause of mesothelioma in regions such as Turkey where exposure to this type of fiber is highly prevalent. Recently, the polyoma virus SV40 has been unexpectedly discovered as an effective cocarcinogen of asbestos in the causation of animal mesothelioma, though despite considerable research, its potential role in human mesothelioma remains unproven.

Jung, S.H. e.a. (2012)

Jung, S.H. e.a. (2012). A decade of malignant mesothelioma surveillance in Korea. Am J Ind Med. 2012 Apr 27. doi: 10.1002/ajim.22065.
Abstract
Background:
The objectives of this study were to examine trends in mesothelioma incidence over a decade and to identify histories of asbestos exposure among cases in Korea.
Methods: In 2001, The Korea Occupational Safety and Health Agency organized a nationwide cardiopulmonary pathology group and established a malignant mesothelioma surveillance system covering all general hospitals in Korea. Mesothelioma cases were reported to this surveillance system with information about age, gender, location, occupational history, asbestos exposure environment, date of diagnosis, diagnostic method, histopathologic subtype, occurrence site, and other clinical information. Additionally, an epidemiological survey was conducted using a structured verbal questionnaire to allow further evaluation of asbestos exposures.
Results: A total of 399 cases of malignant mesothelioma were reported in the last decade, translating to approximately 40 annual cases, and an annual average incidence rate of 0.83 cases per million. Of the 152 patients interviewed by occupational physicians, 56 had occupational asbestos exposure histories (36.8%). Their occupations and industries included construction (19.7%), automobile repair (5.9%), asbestos textile, shipbuilding and repair, refinery work, boiler making, and asbestos cement work. Another 31 patients had environmental asbestos exposure histories.
Conclusions: Surveillance data indicate that malignant mesothelioma incidence in Korea is, thus far, lower than that of other developed countries, and that construction and environmental asbestos exposure were the main identifiable causes of malignant mesothelioma.