Aude Lacourt

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma

Objectives To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. Methods A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. Results A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI −33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. Conclusions Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

Matgene: A Program to Develop Job-Exposure Matrices in the General Population in France

OBJECTIVES Matgéné is a program to develop job-exposure matrices (JEMs) adapted to the general population in France for the period since 1950. The aim is to create retrospective exposure assessment tools for estimating the prevalence of occupational exposure to various agents that can then be correlated to health-related parameters. METHODS JEMs were drawn up by a team of six industrial hygienists who based their assessments on available occupational measurement, economic and statistical data, and several thousand job descriptions from epidemiological studies performed in France since 1984. Each JEM is specific to one agent, assessing exposure for a set of homogeneous combinations (occupation × activity × period) according to two occupational classifications (ISCO 1968 and PCS 1994) and one economic activities classification (NAF 2000). The cells of the JEM carry an estimate of the probability and level of exposure. Level is estimated by the duration and intensity of exposure-linked tasks or by description of the tasks when exposure measurement data are lacking for the agent in question. The JEMs were applied to a representative sample of the French population in 2007, and prevalence for each exposure was estimated in various population groups. All documents and data are available on a dedicated website. RESULTS By the end of 2010, 18 JEMs have been developed and eight are under development, concerning a variety of chemical agents: organic and mineral dust, mineral fibers, and solvents. By implementation in the French population, exposure prevalences were calculated at different dates and for complete careers, and attributable risk fractions were estimated for certain pathologies. Some of these results were validated by comparison with those of other programs. DISCUSSION Initial Matgéné JEMs results are in agreement with the French and international literature, thus validating the methodology. Exposure estimates precision, however, vary between agents and according to the amount of exposure measurement data available. These JEMs are important epidemiological tools, and improving their quality will require investment in occupational health data harvesting, especially in the case of low-level exposures.

Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma.

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 male subjects. 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 yrs and continued to increase until 30 yrs 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.

Occupations and Industries in France at High Risk for Pleural Mesothelioma: A Population-Based Case-Control Study (1998-2002)

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.

Pleural Mesothelioma and Occupational Coexposure to Asbestos, Mineral Wool, and Silica

RATIONALE Occupational coexposure to asbestos and other fibers or particles could modify the carcinogenicity of asbestos with regard to pleural mesothelioma. OBJECTIVES To estimate associations between pleural mesothelioma and occupational mineral wool and silica exposure and to study the impact of occupational coexposure on the risk of pleural mesothelioma. METHODS A total of 1,199 male cases and 2,379 control subjects were included in a French pooled case-control study. Complete job histories were collected, and occupational exposure to asbestos, mineral wool (MW), and silica were assessed by three French job exposure matrices. Unconditional logistic regression models adjusted for age, birth date, and occupational asbestos exposure were used to estimate odds ratios (OR) and 95% confidence intervals (CIs). MEASUREMENTS AND MAIN RESULTS A significant association between mesothelioma and MW exposure was observed after adjustment for occupational asbestos exposure. OR for subjects exposed to less than 0.01 fibers·ml(-1)·yr(-1) was 1.6 (95% CI, 1.2-2.1) and increased to 2.5 (95% CI, 1.8-3.4) for subjects exposed to more than 0.32 fibers·ml(-1)·yr(-1). All ORs for silica exposure were around the null. Coexposure to either asbestos and MW or asbestos and silica seemed to increase the risk of pleural mesothelioma. ORs were 17.6 (95% CI, 11.8-26.2) and 9.8 (95% CI, 4.2-23.2) for subjects exposed to both asbestos and MW and for subjects exposed to both asbestos and silica, respectively, compared with 4.3 (95% CI, 1.9-9.8) for occupational asbestos exposure alone. CONCLUSIONS Our results are in favor of an increased risk of pleural mesothelioma for subjects exposed to both asbestos and MW or asbestos and silica.

Five years update on relationships between malignant pleural mesothelioma and exposure to asbestos and other elongated mineral particles

ABSTRACT Despite the reduction of global asbestos consumption and production due to the ban or restriction of asbestos uses in more than 50 countries since the 1970s, malignant mesothelioma remains a disease of concern. Asbestos is still used, imported, and exported in several countries, and the number of mesothelioma deaths may be expected to increase in the next decades in these countries. Asbestos exposure is the main risk factor for malignant pleural mesothelioma, but other types of exposures are linked to the occurrence of this type of cancer. Although recent treatments improve the quality of life of patients with mesothelioma, malignant pleural mesothelioma remains an aggressive disease. Recent treatments have not resulted in appreciable improvement in survival, and thus development of more efficient therapies is urgently needed. The development of novel therapeutic strategies is dependent on our level of knowledge of the physiopathological and molecular changes that mesothelial cells acquired during the neoplastic process. During the past 5 years, new findings have been published on the etiology, epidemiology, molecular changes, and innovative treatments of malignant pleural mesothelioma. This review aims to update the findings of recent investigations on etiology, epidemiology, and molecular changes with a focus on (1) attributable risk of asbestos exposure in men and women and (2) coexposure to other minerals and other elongated mineral particles or high aspect ratio nanoparticles. Recent data obtained on genomic and gene alterations, pathways deregulations, and predisposing factors are summarized.

Perspectives in Biological Monitoring of Inhaled Nanosized Particles

Given the results of experimental studies, occupational or environmental exposures to manufactured nanoparticles or to unintentionally produced ultrafine particles may result in health effects or diseases in humans. In this review, we synthesize published data of experimental studies on the distribution of inhaled nanoparticles and the first case reports to discuss the potential usefulness of their biological monitoring for clinical purposes. Toxicokinetic studies suggest that nanoparticles may be absorbed predominantly by respiratory and oral routes with possible systemic translocation, leading to accumulation in the peripheral organs or excretion in feces or urine. Some methods used in these studies may be applied successfully in retrospective evaluation of exposure or in follow-up of occupational exposure in the workplace. Biological monitoring of nanoparticles should be based on imaging methods that are essential to confirm their presence and to characterize them in tissue associated with analytical quantitative methods. The first case reports reviewed emphasize the urgent need for the development of standardized procedures for the preparation and analysis of biological samples with a view to characterizing and quantifying nanoparticles.

Dose-time-response association between occupational asbestos exposure and pleural mesothelioma

Objectives Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose–response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case–control study. Methods This study included 1196 male cases recruited in 1987–2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure. Results Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95% CI 2.01 to 2.87)). Conclusion This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk.

Facteurs de risque professionnels du cancer bronchopulmonaire

OBJECTIVE We aimed to review the literature regarding the dose-response relationship between occupational exposure to chemicals classified by the International Agency for Research on Cancer (IARC) as carcinogenic agents and the risk of some lung cancers and on any combined effect with tobacco exposure on lung cancer risk. METHODS A literature search was performed in three databases as well as in the IARC monographs between January 1990 and April 2015. RESULTS The literature is abundant for some carcinogens such as asbestos, crystalline silica and diesel exhaust fumes but is more sparse for many carcinogens and particularly any interaction with tobacco on lung cancer risk. CONCLUSION Few data exist for most lung occupational carcinogens including their interaction with tobacco exposure. In the case of exposure to occupational carcinogens and co-exposure to tobacco smoke, there is a dual primary prevention objective: the elimination of both occupational risk factors and tobacco smoke.

Occupational Asbestos Exposure and Incidence of Colon and Rectal Cancers in French Men: The Asbestos-Related Diseases Cohort (ARDCo-Nut).

Background: The relationships between asbestos exposure and colorectal cancer remain controversial. Objectives: We examined the association between asbestos exposure and colorectal cancer incidence. Methods: Volunteer retired workers previously exposed to asbestos were invited to participate in the French ARDCo screening program between 2003 and 2005. Additional data on risk factors for colorectal cancer were collected from the ARDCo-Nut subsample of 3,769 participants in 2011. Cases of colon and rectal cancer were ascertained each year through 2014 based on eligibility for free medical care following a cancer diagnosis. Survival regression based on the Cox model was used to estimate the relative risk of colon and rectal cancer separately, in relation to the time since first exposure (TSFE) and cumulative exposure index (CEI) to asbestos, and with adjustment for smoking in the overall cohort and for smoking, and certain risk factors for these cancers in the ARDCo-Nut subsample. Results: Mean follow-up was 10.2 years among 14,515 men, including 181 colon cancer and 62 rectal cancer cases (41 and 17, respectively, in the ARDCo-Nut subsample). In the overall cohort, after adjusting for smoking, colon cancer was significantly associated with cumulative exposure (HR = 1.14; 95% CI: 1.04, 1.26 for a 1-unit increase in ln-CEI) and ≥ 20–40 years since first exposure (HR = 4.67; 95% CI: 1.92, 11.46 vs. 0–20 years TSFE), and inversely associated with 60 years TSFE (HR = 0.26; 95% CI: 0.10, 0.70). Although rectal cancer was also associated with TSFE 20–40 years (HR = 4.57; 95% CI: 1.14, 18.27), it was not associated with ln-CEI, but these findings must be interpreted cautiously due to the small number of cases. Conclusions: Our findings provide support for an association between occupational exposure to asbestos and colon cancer incidence in men. Citation: Paris C, Thaon I, Hérin F, Clin B, Lacourt A, Luc A, Coureau G, Brochard P, Chamming’s S, Gislard A, Galan P, Hercberg S, Wild P, Pairon JC, Andujar P. 2017. Occupational asbestos exposure and incidence of colon and rectal cancers in French men: the Asbestos-Related Diseases Cohort (ARDCo-Nut). Environ Health Perspect 125:409–415; http://dx.doi.org/10.1289/EHP153