Occupational exposure to organic solvents and the risk of developing testicular germ cell tumors (TESTIS study): Effect of combined exposure assessment on risk estimation.

OBJECTIVES: Etiological factors of testicular germ cell tumors (TGCT) remain largely unknown, but a causal role of occupational exposures to solvents has been suggested. Previous studies analyzing these exposures reported discordant results, potentially related to exposure assessment methods. The aim of this study was to investigate the role of occupational exposure to solvents on the risk of developing TGCT among young men. METHODS: This study examined occupational exposures to solvents and TGCT risk based on the lifetime work histories of 454 cases and 670 controls, aged 18-45 years, of the French national TESTIS case-control study. Solvent exposure was estimated using: (i) exposure assignment by job-exposure matrix (JEM) and (ii) JEM combined with self-reported exposure data from specific questionnaires (SQ) and expert assessment (EA). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. RESULTS: Both approaches (JEM and JEM+SQ+EA) showed a consistent association between TGCT and trichloroethylene exposure (exposed versus not exposed; JEM=OR 1.80 [95% confidence interval (CI) 1.12-2.90] and JEM+SQ+EA= OR 2.59 (95% CI 1.42-4.72). Both approaches also observed positive associations with ketone esters and fuels & petroleum-based solvents. CONCLUSION: The results suggest that some organic solvents might be involved in the pathogenesis of TGCT among occupationally exposed men. The combined use of JEM+SQ+EA seemed to limit misclassification by considering individual exposure variability and is, therefore, an appealing approach to assess occupational exposures in epidemiological studies.

Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort.

OBJECTIVES: The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012-2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. RESULTS: In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. CONCLUSIONS: Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

Occupational exposure to silica dust in France: an ongoing concern.

OBJECTIVES: Crystalline silica is found in many construction materials. Although it is one of the oldest known occupational exposures, new exposure contexts have emerged in recent years. In 2021, France classified work involving exposure to respirable crystalline silica (ie, silica dust) generated by a work process as carcinogenic. In order to assess exposure in the French workforce between 1947 and 2020, we developed a silica job-exposure matrix (JEM) for the Matgéné program. METHOD: The JEM was linked with occupational data from different population censuses (1982, 1990, 1999, 2007 and 2017). The proportions and numbers of workers exposed to silica dust in France at these various census time points were estimated and described by sex and industry for 2017. RESULTS: After decreasing between 1982 and 1999, the proportion of workers exposed to silica dust remained stable at 4%, representing 975 000 workers in 2017. Exposed workers were mostly men (93%), and most worked in the construction industry (64%). This was also the industry where the majority of workers were exposed to a level above the French 8-hour time weighted average occupational exposure limit (TWA-OEL). CONCLUSION: A large number of workers in France were still exposed (some highly) to silica dust in 2017 so this agent still poses an occupational health concern. The results of this study provide key information about the continued surveillance of the evolution of exposure to silica dust. In a few years, it will be possible to quantify the impact of the 2021 regulation in terms of proportions and number of workers exposed to silica dust.

Parental occupational exposure to solvents and risk of developing testicular germ cell tumors among sons: a French nationwide case-control study (TESTIS study).

OBJECTIVES: The etiology of testicular germ cell tumors (TGCT) is suspected to be related to prenatal environmental risk factors. Some solvents have potential endocrine disrupting or carcinogenic properties and may disrupt male genital development in utero. The aim of this study was to examine the association between parental occupational exposure to solvents and TGCT risk among their offspring. METHODS: A French nationwide case-control study, TESTIS included 454 TGCT cases and 670 controls frequency-matched on region and 5-year age strata. Participants were interviewed via telephone and provided information on parental occupations at birth. Job-exposure matrices (JEM) developed in the French Matgéné program were used to assign exposure to five petroleum-based solvents, five solvents or groups of oxygenated solvents, and five chlorinated solvents. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors. RESULTS: Occupational exposure to at least one solvent during the year of their son's birth was 41% among fathers and 21% among mothers. Paternal exposure to at least one solvent showed OR 0.89 (95% CI 0.68-1.15). Exposure to perchloroethylene (OR 1.41, 95% CI 0.55-3.61), methylene chloride (OR 1.13, 95% CI 0.54-2.34) and diesel/kerosene/fuel oil (OR 1.17, 95% CI 0.80-1.73) disclosed OR >1 but with low precision. Our results suggest a possible modest increase in non-seminoma risk for sons whose fathers were highly exposed to trichloroethylene (OR 1.44, 95% CI 0.79-2.63). Maternal exposure to at least one solvent showed OR 0.90 (95% CI 0.65-1.24). When stratifying by birth year, men born in the 1970s experienced an increased TGCT risk following maternal exposure to fuels and petroleum-based solvents (OR 2.74, 95% CI 1.11-6.76). CONCLUSION: Overall, no solid association was found between parental occupational exposure to solvents and TGCT risk. The association found with maternal occupational exposure to fuels and petroleum solvents among older men needs further investigation.

Wood dust in France. Trends in the population of exposed workers between 1982 and 2017 based on a job-exposure matrix assessment.

OBJECTIVE: Many occupations and industries use wood as a raw material and wood dust is a well-known carcinogen. This study presents trends in occupational exposure to wood dust for all workers (employees and self-employed workers) in France between 1982 and 2017 and focuses on the exposed workers in 2017. METHODS: Exposures to this carcinogen were assessed using the Matgéné job-exposure matrix. Trends in the prevalence and proportion of exposure over the study period were estimated by linking the matrix with population data from the 1982, 1990, 1999, 2007, and 2017 censuses and are described for selected industry groups. RESULTS: The number of exposed workers to wood dust has decreased significantly over the last 40 years, from 466,900 potentially exposed workers in 1982 to 305,000 workers in 2017. The proportion of exposed workers has also decreased over time, although not uniformly across industries. Increases in the proportion of exposed workers are observed in certain industries, such as "Sawmilling and logging" (from 61.2% to 73.6% over the period for men) and "Finishing of sale premises" (from 3.3% to 6.2% for women). CONCLUSION: This article is the first to describe occupational exposure to wood dust in France for all workers and to follow its evolution over the last 40 years. Occupations and industries still at risk in 2017 are also described with the aim of helping to improve prevention policies.

Estimated number of cancers attributable to occupational exposures in France in 2017: an update using a new method for improved estimates.

BACKGROUND: Over the last 50 years, occupational exposure to carcinogenic agents has been widely regulated in France. OBJECTIVE: Report population-attributable fraction (PAF) and number of attributable cancer cases linked to occupational exposure in France based on an updated method to estimate lifetime occupational exposure prevalence. METHODS: Population-level prevalence of lifetime exposure to ten carcinogenic agents (asbestos, benzene, chromium VI, diesel engine exhaust, formaldehyde, nickel compounds, polycyclic aromatic hydrocarbons, silica dust, trichloroethylene, wood dust) and two occupational circumstances (painters and rubber industry workers) were estimated using the French Census linked with MATGÉNÉ job-exposure matrices and French occupational surveys. PAF and number of attributable cancer cases were calculated using the estimated prevalence, relative risks from systematic review and national estimates of cancer incidence in 2017. RESULTS: The lifetime occupational exposure prevalences were much higher in men than in women ranging from 0.2% (workers in the rubber industry) to 10.2% in men (silica), and from 0.10% (benzene, PAH and workers in the rubber industry) to 5.7% in women (formaldehyde). In total, 4,818 cancer cases (men: 4,223; women: 595) were attributable to the ten studied carcinogens and two occupational circumstances, representing 5.2% of cases among the studied cancer sites (M: 7.0%; W: 1.9%). In both sexes, mesothelioma (M: 689 cases; W: 160) and lung cancer (M: 3,032; W: 308) were the largest cancer sites impacted by the studied occupational agents and circumstances. SIGNIFICANCE: A moderate proportion of the cancer cases in France is linked to carcinogens in occupational settings. Our method provides more precise estimates of attributable cancer taking into account evolution of exposure to occupational agents by sex, age and time. This methodology can be easily replicated using cross-sectional occupational data to aid priority making and implementation of prevention strategies in the workplace.

A 34-year overview of night work by occupation and industry in France based on census data and a sex-specific job-exposure matrix.

BACKGROUND: Night work has been increasing in the last decades due to new working arrangements for good and services production. Numerous studies have shown that night shift work causes disruptions in circadian rhythms that may affect health. In 2019, night shift work was classified as probably carcinogenic to humans by the International Agency for Research on Cancer, and may contribute to other health disorders. In this context, we assessed the number and proportion of workers exposed to night work today and investigated time trends by occupation and industry in France since 1982 in terms of prevention. METHODS: Using the data on work time schedules collected in the French Labour Force Surveys, sex- and period-specific job-exposure matrices (JEMs) to night work (working between midnight and 5 AM) were developed. After linkage of the JEMs with data of the national censuses of 1982, 1990, 1999, 2007 and 2015, the numbers and proportions of workers usually or occasionally exposed to night work were estimated. RESULTS: The number of night workers (usual and occasional) increased from 3.67 million in 1982 to 4.37 million in 2015 (15.8% vs 16.4%). Night work was more common in men than in women (e.g. 22.4% vs 10.0% in 2015), and usual night work largely increased after 2000 (4.4% in 1999, 7.2% in 2007). In 2015, 1.29 million men worked usually at night, including 882,000 workers in the service sector (63%) and 360,000 in the manufacturing and extracting industries (28%). For the same period, 581,000 women were usual night workers, most of them being employed in the service sector (90%). Among women, a 97% increase of usual night work was observed between 1982 and 2015. CONCLUSIONS: This study shows that night work involves a growing number of workers in France, particularly in women in the service sector. These results raise concern about the public health impact of night work and particularly about the numbers of outcomes attributable to this exposure such as breast or prostate cancers.

Association Between Occupational Exposure to Formaldehyde and Cognitive Impairment.

BACKGROUND AND OBJECTIVES: To our knowledge, no study has investigated the effect of exposure to formaldehyde on cognition in the general population. Our objective was to examine the association between occupational exposure to formaldehyde and cognitive impairment in middle-aged and young-old adults (≥45 years). METHODS: In the French CONSTANCES cohort, cognitive function was assessed with a standardized battery of 7 cognitive tests to evaluate global cognitive function, episodic verbal memory, language abilities, and executive functions (e.g., Digit Symbol Substitution Test [DSST]). A global cognitive score was created using principal component analysis. Cognitive impairment was assessed in reference to norms of neuropsychological battery according to age, sex, and education. Lifetime exposure to formaldehyde was assessed using a French Job Exposure Matrix created in the framework of the Matgéné project. After performing multiple imputation, separate modified Poisson regression models were used to evaluate the association between cognitive impairment (<25th percentile) and formaldehyde exposure (exposed/never exposed), exposure duration, cumulative exposure index (CEI), and combination of CEI and time of last exposure. RESULTS: Among 75,322 participants (median age 57.5 years, 53% women), 8% were exposed to formaldehyde during their professional life. These participants were at higher risk of global cognitive impairment (for global cognitive score: adjusted relative risk [aRR] 1.17; 95% confidence interval [CI] 1.11-1.23), after adjusting for confounders (age, sex, education, income, solvent exposure, Effort-Reward Imbalance, night shift, repetitive work, and noisy work). They were at higher risk of cognitive impairment for all cognitive domains explored. Longer exposure duration and high CEI were associated with cognitive impairment, with a dose-effect relationship for exposure duration. Recent exposure was associated with impairment in all cognitive domains. Time did not fully attenuate formaldehyde-associated cognitive deficits especially in highly exposed individuals (for DSST: high past exposure aRR 1.23; 95% CI 1.11-1.36; high recent exposure: aRR 1.24; 95% CI 1.13-1.35). DISCUSSION: Our findings highlight the long-term detrimental effect of formaldehyde exposure on cognitive health in a relatively young population.

COVID-19 hotspots through clusters analysis in France (may-October 2020): where should we track the virus to mitigate the spread?

BACKGROUND: In France, the lifting of the lockdown implemented to control the COVID-19 first wave in 2020 was followed by a reinforced contact-tracing (CT) strategy for the early detection of cases and transmission chains. We developed a reporting system of clusters defined as at least three COVID-19 cases, within seven days and belonging to the same community or having participated in the same gathering, whether they know each other or not. The aim of this study was to describe the typology and criticality of clusters reported between the two lockdowns in France to guide future action prioritisation. METHODS: In this study we describe the typology and criticality of COVID-19 clusters between the two lockdowns implemented in France (between May and end of October 2020). Clusters were registered in a national database named "MONIC" (MONItoring des Clusters), established in May 2020. This surveillance system identified the most affected communities in a timely manner. A level of criticality was defined for each cluster to take into consideration the risk of spreading within and outside the community of occurrence, and the health impact within the community. We compared the level of criticality according to the type of community in which the cluster occurred using Pearson's chi-square tests. RESULTS: A total of 7236 clusters were reported over the study period, particularly in occupational environment (25.1%, n = 1813), elderly care structures (21.9%, n = 1586), and educational establishments (15.9%, n = 1154). We show a shift over time of the most affected communities in terms of number of clusters. Clusters reported in occupational environment and the personal sphere had increased during summer while clusters reported in educational environment increased after the start of the school year. This trend mirrors change of transmission pattern overtime according to social contacts. Among all reported clusters, 43.1% had a high level of criticality with significant differences between communities (p < 0.0001). A majority of clusters had a high level of criticality in elderly care structures (82.2%), in disability care centres (56.6%), and health care facilities (51.7%). CONCLUSION: These results highlight the importance of targeting public health action based on timely sustained investigations, testing capacity and targeted awareness campaigns. The emergence of new SARS-CoV-2 variants strengthen these public health recommendations and the need for rapid and prioritise vaccination campaigns.

Lifetime occupational exposure proportion estimation methods: a sensitivity analysis in the general population.

OBJECTIVE: To present a sensitivity analysis of the most widely used means of estimating lifetime occupational exposure proportion (LOEP) and their respective impacts on LOEP and population-attributable fraction (PAF) estimates. METHODS: A French population-based sample with full job history (N = 10,010) was linked with four Matgéné job-exposure matrices: flour, cement, silica and benzene. LOEP and the 95% confidence interval were estimated using four methods: the maximum exposure probability during the career (Proba_max), two methods subdividing careers into job-periods (job-period_M1, job-period_M2) and one into job-years (job-year). To quantify differences between methods, percentages of variation were calculated for proportion values and PAF, and compared with published results for France using cross-sectional proportion multiplied by a factor. RESULTS: For each agent, LOEP estimated from the maximum probability during the career (Proba_max) was consistently lower than proportion taking account of job-periods or job-years. LOEP on Proba_max for flour, cement, silica and benzene were, respectively, 4.4% 95% CI (4.0-4.7), 4.3% (3.9-4.6), 6.1% (5.7-6.5) and 3.9% (3.6-4.2). Percentage of variation ranged from 0 to 55.8% according to the agent. The number of cancer cases varied by a twofold factor for exposure to silica and lung cancer and by a fourfold factor for exposure to benzene and acute myeloid lymphoma. CONCLUSIONS: The present study provides a description of several LOEP estimation methods based on exposure assessment over the entire career and describes their impact on PAF. For health monitoring purposes, we recommend to report a range of LOEP with low and high estimates obtained using job-periods (job-period_M1 and job-period_M2).

An innovative method to estimate lifetime prevalence of carcinogenic occupational circumstances: the example of painters and workers of the rubber manufacturing industry in France.

BACKGROUND: Existing methods to estimate lifetime exposure to occupational carcinogenic agents could be improved. OBJECTIVE: We propose a new method to estimate the lifetime prevalence of exposure to occupational carcinogens using the example of painters and workers of the rubber industry in France. METHODS: From census, we calculated the proportion of painters and rubber industry workers using predefined occupational codes related to each occupation by sex and 10-year age group in 1982, 1990, 1999, 2007, and 2013. Using a beta-regression model, we obtained the yearly prevalence of exposure by 10-year age group over the period 1967-2007. We estimated the age- and sex-specific lifetime prevalence of exposure of the population in 2017 over 1967-2007, summing up the estimated prevalence of exposure for years 1967, 1977, 1987, 1997, and 2007 combined with a sex- and age-specific turnover factor. Corresponding population-attributable fractions were estimated for lung and bladder cancers in 2017. RESULTS: In 2017, we estimated that 5.6 and 0.2% of men in France had ever worked as a painter or in the rubber industry, respectively, during their working time. The lifetime prevalence of ever having worked as a painter or in the rubber industry was much lower in women: 1.8% and 0.1%, respectively. We estimated that 950 lung cancer and 40 bladder cancer cases were attributable to these occupations in 2017. SIGNIFICANCE: Based on accurate data and taking into account evolution of specific jobs over time, the proposed method provides good estimates of lifetime prevalence of exposure to occupational carcinogens. It could be applied in any other country with similar data.

Occupational exposure to petroleum-based and oxygenated solvents and oral and oropharyngeal cancer risk in men: A population-based case-control study in France.

OBJECTIVE: To examine the association between occupational exposure to petroleum-based and oxygenated solvents and the risk of oral and oropharyngeal cancer. METHODS: The ICARE study is a large population-based case-control study conducted in France between 2001 and 2007. This present analysis was restricted to men and included 350 and 543 cases of squamous cell-carcinoma of the oral cavity and oropharynx, respectively, and 2780 controls. Lifetime tobacco, alcohol consumption and complete occupational history were assessed through detailed questionnaires. Job-exposure matrices allowed us to assess occupational exposure to five petroleum-based solvents (white spirits; diesel/fuel oils/kerosene; gasoline; benzene; special petroleum products) and five oxygenated solvents (diethyl ether; tetrahydrofuran; ketones and esters; alcohols; ethylene glycol). Odds-ratios (ORs), adjusted for age, smoking, alcohol consumption and socioeconomic status, and 95% confidence intervals (CI) were estimated using unconditional logistic models. RESULTS: Associations between oral cancer risk and exposure to white spirits and diesel/fuel oils/kerosene were suggested, but there was no exposure-response trend. Concerning exposure to oxygenated solvents, participants with the highest levels of cumulative exposure to diethyl ether had a significant excess risk of oropharyngeal cancer (OR = 7.78, 95%CI 1.42 to 42.59; p for trend = 0.04). Ever exposure to tetrahydrofuran was associated with a borderline significant increased risk of oral cancer (OR = 1.87, 95%CI 0.97 to 3.61), but no exposure-response trend was observed. Additional adjustments for exposure to other solvents did not substantially change the results. CONCLUSION: Our results do not provide evidence for a major role of petroleum-based and oxygenated solvents in the occurrence of oral and oropharyngeal cancers in men.

Occupational exposure to flour dust and the risk of head and neck cancer.

BACKGROUND: To investigate the association between head and neck squamous cell cancer (HNSCC) risk and occupational exposure to flour dust in women and men, using data from ICARE, a French population-based case-control study. METHODS: The analysis included 2053 cases of HNSCC and 3507 controls. Lifelong occupational history was collected. A job-exposure matrix was used to assess exposure to flour dust. Odds-ratios (ORs) and 95% confidence intervals (CI), adjusted for smoking, alcohol drinking, and asbestos exposure, were estimated with logistic regression models. RESULTS: Ever exposure to flour dust was associated with elevated ORs in women (OR = 2.15, 95%CI: 1.01 4.55) and in men (OR = 1.55, 95%CI: 1.11 2.17). In women, the risk increased with the probability, the duration, and the cumulative level of exposure. No dose-response relationships were observed in men. CONCLUSIONS: Although the results were less conclusive in men than in women, overall, these findings provide some support to the hypothesis of a role of flour dust in the occurrence of HNSCC.

Development of a Coding and Crosswalk Tool for Occupations and Industries.

Introduction: Job coding into a standard occupation or industry classification is commonly performed in occupational epidemiology and occupational health. Sometimes, it is necessary to code jobs into multiple classifications or to convert job codes from one classification to another. We developed a generic tool, called CAPS-Canada (http://www.caps-canada.ca/), that combines a computer-assisted coding tool covering seven International, Canadian and US occupation and industry classifications and an assistant facilitating crosswalks from one classification to another. The objectives of this paper are to present the different functions of the CAPS-Canada tool and to assess their contribution through an inter-rater reliability study. Method: The crosswalk assistant was built based on a database of >30,000 jobs coded during a previous project. We evaluated to what extent it would allow automatic translation between pairs of classifications. The influence of CAPS-Canada on agreement between coders was assessed through an inter-rater reliability study comparing three approaches: manual coding, coding with CAPS-Canada without the crosswalk assistant, and coding with the complete tool. The material for this trial consisted of a random sample of 1000 jobs extracted from a case-control study and divided into three subgroups of equivalent size. Results: Across the classification systems, the crosswalk assistant would provide useful information for 83-99% of jobs (median 95%) in a population similar to ours. Eighteen to eighty-one percent of jobs (median 56%) could be entirely automatically recoded. Based on our sample of 1000 jobs, inter-rater reliability in occupation coding ranged from 35.7 to 66.5% (median 53.7%) depending on the combination of classification/resolution. Compared with manual coding, the use of CAPS-Canada substantially improved inter-rater reliability. Conclusion: CAPS-Canada is an attractive alternative to manual coding and is particularly relevant for coding a job into multiple classifications or for recoding jobs into other classifications.

Risk factors for salivary gland cancers in France: Results from a case-control study, the ICARE study.

OBJECTIVES: Epidemiological studies on the risk factors for salivary gland cancers (SGC) are rare, concern a small sample size, and show inconsistent results. The aim of the present work was to analyze several risk factors for SGC, using the data from the ICARE study, a multicenter, population-based case-control study. MATERIALS AND METHODS: Data from 73 SGC cases and 3555 controls were collected using a standardized questionnaire on lifestyle habits, personal and family medical history, and lifetime occupational history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regressions. RESULTS: Tobacco use and alcohol consumption were not associated with the risk of SGC. A history of head and neck cancer or that of cervicofacial radiotherapy was associated with a higher risk of SGC (OR = 17.06, 95% CI: 4.34-67.05, and OR = 31.74, 2.48-405.25, respectively). Significantly increased risks were observed for some occupations: waiter (OR = 2.94, 1.11-7.78), charworker (OR = 3.02, 1.38-6.60), electrical and electronic equipment assembler (OR = 7.16, 2.02-25.38), plumber (OR = 3.95, 1.33-11.67), electric arc welder (OR = 6.15, 1.76-21.48), sheet-metal worker (OR = 2.89, 1.01-8.32), building painter (OR = 3.42, 1.01-11.49), and material handling equipment operator (OR = 5.05, 1.71-14.84). Results for industries were consistent with those observed for occupations. CONCLUSION: Our results showed that a history of head and neck cancer, cervicofacial radiotherapy, and several occupations and industries, were associated with an increased risk of SGC. Further studies with larger sample sizes are indicated to confirm our results.

Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France: the ICARE study.

BACKGROUND: To examine associations between occupational exposure to petroleum-based and oxygenated solvents and the risk of hypopharyngeal and laryngeal cancer. METHODS: ICARE is a large, frequency-matched population-based case-control study conducted in France. Lifetime occupational history, tobacco smoking and alcohol consumption were collected. Analyses were restricted to men and included 383 cases of hypopharyngeal cancer, 454 cases of laryngeal cancer, and 2780 controls. Job-exposure matrices were used to assess exposure to five petroleum-based solvents (benzene; gasoline; white spirits; diesel, fuels and kerosene; special petroleum products) and to five oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). Odds ratios (ORs) adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals (CI) were estimated with unconditional logistic models. RESULTS: No significant association was found between hypopharyngeal or laryngeal cancer risk and exposure to the solvents under study. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of white spirits (OR = 1.46; 95% CI: 0.88-2.43) and tetrahydrofuran (OR = 2.63; 95CI%: 0.55-12.65), with some indication of a dose-response relationship (p for trend: 0.09 and 0.07 respectively). CONCLUSION: This study provides weak evidence for an association between hypopharyngeal cancer and exposure to white spirits and tetrahydrofuran, and overall does not suggest a substantial role of exposure to petroleum-based or oxygenated solvents in hypopharyngeal or laryngeal cancer risk.

Occupational exposure to organic solvents and risk of male breast cancer: a European multicenter case-control study.

Objectives The etiology of male breast cancer (MBC) is largely unknown but a causal role of exposure to organic solvents has been suggested. Previous studies on occupational risk factors of breast cancer were often restricted to women who are frequently exposed to lower levels and at a lower frequency than men. We investigated the association between MBC and occupational exposure to petroleum and oxygenated and chlorinated solvents in a multicenter case-control study of rare cancers in Europe. Methods The study included 104 MBC cases and 1901 controls. Detailed lifetime work history was obtained during interviews, together with sociodemographic characteristics, medical history and lifestyle factors. Occupational exposures to solvents were estimated from a job-exposure matrix. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results Lifetime cumulative exposure to trichloroethylene >23.9 ppm years was associated with an increased MBC risk, compared to non-exposure [OR (95% CI): 2.1 (1.2-4.0); P trend <0.01). This increase in risk persisted when only exposures that occurred ≥10 years before diagnosis were considered. In addition, a possible role for benzene and ethylene glycol in MBC risk was suggested, but no exposure-response trend was observed. Conclusions These findings add to the evidence of an increased risk of breast cancer among men professionally exposed to trichloroethylene and possibly to benzene or ethylene glycol. Further studies should be conducted in populations with high level of exposure to confirm our results.

Occupational exposure to chlorinated solvents and risk of head and neck cancer in men: a population-based case-control study in France.

BACKGROUND: Few epidemiological studies have investigated the link between occupational exposure to solvents and head and neck cancer risk, and available findings are sparse and inconsistent. The objective of this study was to examine the association between occupational exposure to chlorinated solvents and head and neck cancer risk. METHODS: We analyzed data from 4637 men (1857 cases and 2780 controls) included in a population-based case-control study, ICARE (France). Occupational exposure to five chlorinated solvents (perchloroethylene [PCE], trichloroethylene [TCE], methylene chloride [MC], chloroform [CF], and carbon tetrachloride [CT]) was assessed through job-exposure matrices. Odds ratios (ORs) and confidence intervals (95% CI) were estimated by unconditional logistic regression, adjusted for age, tobacco smoking, alcohol consumption, asbestos exposure, and other potential confounders. RESULTS: We observed no association between chlorinated solvent exposure and head and neck cancer risk, despite a non-significant increase in risk among subjects who had the highest cumulative level of exposure to PCE, (OR = 1.81; 95% CI = 0.68 to 4.82). In subsite analysis, the risk of laryngeal cancer increased with cumulative exposure to PCE (p for trend = 0.04). The OR was 3.86 (95% CI = 1.30 to 11.48) for those exposed to the highest levels of PCE. A non-significant elevated risk of hypopharyngeal cancer was also observed in subjects exposed to the highest levels of MC (OR = 2.36; 95% CI = 0.98 to 5.85). CONCLUSION: Our findings provide evidence that high exposure to PCE increases the risk of laryngeal cancer, and suggest an association between exposure to MC and hypopharyngeal cancer. Exposure to other chlorinated solvents was not associated with the risk of head and neck cancer.

Occupational exposure to solvents and risk of head and neck cancer in women: a population-based case-control study in France.

OBJECTIVE: Our objective was to investigate the association between head and neck cancer and occupational exposure to chlorinated, oxygenated and petroleum solvents in women. METHODS: Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE), a French population-based case-control study, included 296 squamous cell carcinomas of the head and neck (HNSCC) in women and 775 female controls. Lifelong occupational history was collected. Job-exposure matrices allowed to assess exposure to 5 chlorinated solvents (carbon tetrachloride; chloroform; methylene chloride; perchloroethylene; trichloroethylene), 5 petroleum solvents (benzene; special petroleum product; gasoline; white spirits and other light aromatic mixtures; diesel, fuels and kerosene) and 5 oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). OR and 95% CIs, adjusted for smoking, alcohol drinking, age and geographical area, were estimated with logistic models. RESULTS: Elevated ORs were observed among women ever exposed to perchloroethylene (OR=2.97, 95% CI 1.05 to 8.45) and trichloroethylene (OR=2.15, 95% CI 1.21 to 3.81). These ORs increased with exposure duration (OR=3.75, 95% CI 0.64 to 21.9 and OR=4.44, 95% CI 1.56 to 12.6 for 10 years or more, respectively). No significantly increased risk of HNSCC was found for occupational exposure to the other chlorinated, petroleum or oxygenated solvents. CONCLUSIONS: These findings suggest that exposure to perchloroethylene or trichloroethylene may increase the risk of HNSCC in women. In our study, there is no clear evidence that the other studied solvents are risk factors for HNSCC.

Multidimensional analysis of the effect of occupational exposure to organic solvents on lung cancer risk: the ICARE study.

BACKGROUND: The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances. OBJECTIVES: The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos. METHODS: We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case-control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression. RESULTS: After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters. CONCLUSIONS: Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk.