Frequency of Asbestos Exposure and Histological Subtype of Ovarian Carcinoma.

The International Agency for Research on Cancer established a causal link between asbestos exposure and ovarian cancer. However, the exposure frequency and histological characteristics of asbestos-associated ovarian cancers remain to be investigated in detail. This multicenter case-case study assessed the asbestos exposure in ovarian carcinoma (OC) patients, alongside its association with histological subtype. Women were recruited in four hospitals in Lyon, France. Histological reports were reviewed by a pathologist. Patient and family members' data were collected by phone-based questionnaires. Asbestos exposure was defined as direct (occupational and environmental) and indirect (via parents, partners, and children). An industrial hygienist assessed the probability and level of exposure. The 254 enrolled patients (mean age 60 years) reported having an average of 2.3 different jobs (mean working duration 29 years). The prevalence of direct and indirect asbestos exposure was 13% (mean exposure duration 11 years) and 46%, respectively. High-grade serous carcinoma accounted for 73% of all OCs and 82% of histological subtypes in women with direct exposure. After adjustment on a familial history of OC, no significant associations between asbestos exposure (direct and/or indirect) and high-grade serous carcinoma were found. Women with OC had a high prevalence of asbestos exposure. Establishing risk profiles, as reported here, is important in facilitating compensation for asbestos-related OCs and for the surveillance of women at risk.

Welding and the risk of head and neck cancer: the ICARE study.

OBJECTIVE: To investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study. METHODS: Analyses were restricted to men (2703 controls and 1588 cases of squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx). Welding activity and potential confounders were assessed by detailed questionnaires. ORs and CIs (95% CI) were estimated by unconditional logistic regression, adjusted for age, area of residence, tobacco smoking, alcohol consumption and occupational exposure to asbestos. RESULTS: Welding was associated with an increased risk of head and neck cancer overall (OR=1.31, 95% CI 1.03 to 1.67). The association was strongest for laryngeal cancer (OR=1.66, 95% CI 1.15 to 2.38) and the risk increased with the cumulative duration (p-trend <0.01) and the weighted duration (p-trend <0.01) of welding. A cumulative duration and a weighted duration of welding of more than 10 years were also associated with a significantly increased risk of oral cancer (OR=1.82, 95% CI 1.09 to 3.04; OR=2.10, 95% CI 0.99 to 4.45, respectively). A long duration of arc welding was associated with laryngeal cancer, whereas a long duration of spot welding was associated with oral cancer. Welding was not associated with the risk of oropharyngeal and hypopharyngeal cancer. CONCLUSION: Our findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.

Occupational exposure to wood dust and risk of lung cancer: the ICARE study.

OBJECTIVES: In a previous analysis of data from a French population-based case-control study (the Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE) study), 'having ever worked' in wood-related occupations was associated with excess lung cancer risk after adjusting for smoking but not for occupational factors. The present study aimed to investigate the relationship between lung cancer risk and wood dust exposure after adjusting for occupational exposures. METHODS: Data were obtained from 2276 cases and 2780 controls on smoking habits and lifelong occupational history, using a standardised questionnaire with a job-specific questionnaire for wood dust exposure. Logistic regression models were used to calculate ORs and 95% CIs adjusted for age, area of residence, tobacco smoking, the number of job periods and exposure to silica, asbestos and diesel motor exhaust (DME). RESULTS: No significant association was found between lung cancer and wood dust exposure after adjustment for smoking, asbestos, silica and DME exposures. The risk of lung cancer was slightly increased among those who were exposed to wood dust more than 10 years, and had over 40 years since the first exposure. CONCLUSION: Our findings do not provide a strong support to the hypothesis that wood dust exposure is a risk factor for lung cancer. This study showed the importance of taking into account smoking and occupational coexposures in studies on lung cancer and wood dust exposure. Further studies evaluating the level and frequency of exposure during various tasks in woodwork are needed.

Quantifying the mediating effects of smoking and occupational exposures in the relation between education and lung cancer: the ICARE study.

Smoking only partly explains the higher lung cancer incidence observed among socially deprived people. Occupational exposures may account for part of these inequalities, but this issue has been little investigated. We investigated the extent to which smoking and occupational exposures to asbestos, silica and diesel motor exhaust mediated the association between education and lung cancer incidence in men. We analyzed data from a large French population-based case-control study (1976 lung cancers, 2648 controls). Detailed information on lifelong tobacco consumption and occupational exposures to various carcinogens was collected. We conducted inverse probability-weighted marginal structural models. A strong association was observed between education and lung cancer. The indirect effect through smoking varied by educational level, with the strongest indirect effect observed for those with the lowest education (OR = 1.34 (1.14-1.57)). The indirect effect through occupational exposures was substantial among men with primary (OR = 1.22 (1.15-1.30) for asbestos and silica) or vocational secondary education (OR = 1.18 (1.12-1.25)). The contribution of smoking to educational differences in lung cancer incidence ranged from 22 % (10-34) for men with primary education to 31 % (-3 to 84) for men with a high school degree. The contribution of occupational exposures to asbestos and silica ranged from 15 % (10-20) for men with a high school degree to 20 % (13-28) for men with vocational secondary education. Our results highlight the urgent need for public health policies that aim at decreasing exposure to carcinogens at work, in addition to tobacco control policies, if we want to reduce socioeconomic inequalities in the cancer field.

SYN-JEM: A Quantitative Job-Exposure Matrix for Five Lung Carcinogens.

OBJECTIVE: The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons (by its proxy benzo(a)pyrene (BaP)) and respirable crystalline silica). A quantitative job-exposure matrix (JEM) was developed based on statistical modeling of large quantities of personal measurements. METHODS: Empirical linear models were developed using personal occupational exposure measurements (n = 102306) from Europe and Canada, as well as auxiliary information like job (industry), year of sampling, region, an a priori exposure rating of each job (none, low, and high exposed), sampling and analytical methods, and sampling duration. The model outcomes were used to create a JEM with a quantitative estimate of the level of exposure by job, year, and region. RESULTS: Decreasing time trends were observed for all agents between the 1970s and 2009, ranging from -1.2% per year for personal BaP and nickel exposures to -10.7% for asbestos (in the time period before an asbestos ban was implemented). Regional differences in exposure concentrations (adjusted for measured jobs, years of measurement, and sampling method and duration) varied by agent, ranging from a factor 3.3 for chromium-VI up to a factor 10.5 for asbestos. CONCLUSION: We estimated time-, job-, and region-specific exposure levels for four (asbestos, chromium-VI, nickel, and RCS) out of five considered lung carcinogens. Through statistical modeling of large amounts of personal occupational exposure measurement data we were able to derive a quantitative JEM to be used in community-based studies.

Welding, a risk factor of lung cancer: the ICARE study.

OBJECTIVES: We investigated the relationship between lung cancer and occupational exposure to welding activity in ICARE, a population-based case-control study. METHODS: Analyses were restricted to men (2276 cases, 2780 controls). Welding exposure was assessed through detailed questionnaires, including lifelong occupational history. ORs were computed using unconditional logistic regression, adjusted for lifelong cigarette smoking and occupational exposure to asbestos. RESULTS: Among the regular welders, welding was associated with a risk of lung cancer (OR=1.7, 95% CI 1.1 to 2.5), which increased with the duration (OR=2.0, 95% CI 1.0 to 3.9 when duration >10 years), and was maximum 10-20 years since last welding. The risk was more pronounced in case of gas welding (OR=2.0, 95% CI 1.2 to 3.3), when the workpiece was covered by paint, grease, or other substances (OR=2.0, 95% CI 1.2 to 3.4) and when it was cleaned with chemical substances before welding. No statistically significant increase in lung cancer risk was observed among occasional welders. CONCLUSIONS: Although these results should be confirmed, we showed that type of welding and mode of workpiece preparation are important determinants of the lung cancer risk in regular welders.

The joint effect of asbestos exposure, tobacco smoking and alcohol drinking on laryngeal cancer risk: evidence from the French population-based case-control study, ICARE.

OBJECTIVE: The objective of the study was to investigate the joint effect of occupational exposure to asbestos, and tobacco and alcohol consumption, on the risk of laryngeal cancer among men. METHODS: We used data from a large population-based case-control study conducted in France. We estimated two-way and three-way interactions between asbestos exposure (never vs ever exposed), tobacco consumption (<20 vs. ≥20 pack-years) and alcohol consumption (<5 vs. ≥5 drinks per day). The interaction on an additive scale was assessed by estimating the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction, and the interaction on a multiplicative scale was assessed by estimating the multiplicative interaction parameter (ψ). Multiplicative interactions were also assessed using fractional polynomials for alcohol drinking, tobacco smoking and asbestos exposure. RESULTS: When compared with light-to-moderate smokers and drinkers never exposed to asbestos, the increase in laryngeal cancer risk was smallest among light-to-moderate drinkers and smokers exposed to asbestos (OR=2.23 (1.08 to 4.60)), and highest among heavy smokers and drinkers ever exposed to asbestos (OR=69.39 (35.54 to 135.5)). We found an additive joint effect between asbestos exposure and alcohol consumption (RERI=4.75 (-4.29 to 11.12)), whereas we observed a more than additive joint effect between asbestos exposure and tobacco consumption (RERI=8.50 (0.71 to 23.81)), as well as between asbestos exposure, and tobacco and alcohol consumption (RERI=26.57 (11.52 to 67.88)). However, our results did not suggest any interaction on a multiplicative scale. CONCLUSIONS: Our results suggest that asbestos exposure, in combination with tobacco and alcohol exposure, accounted for a substantial number of laryngeal cancer cases. Our findings therefore highlight the need for prevention in activities, such as construction work, where exposure to asbestos-containing materials remains.

Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study.

Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent.

Maternal occupation during pregnancy, birth weight, and length of gestation: combined analysis of 13 European birth cohorts.

OBJECTIVES: We assessed whether maternal employment during pregnancy - overall and in selected occupational sectors - is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design. METHODS: We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity. RESULTS: Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (OR adj) 0.86, 95% confidence interval (95% CI) 0.81-0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (OR adj0.91, 95% CI 0.84-0.99) whereas food industry workers had an increased risk of preterm delivery (OR adj1.50, 95% CI 1.12-2.02). There was little evidence for heterogeneity between cohorts. CONCLUSIONS: This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development.

Occupation and head and neck cancer in women-Results of the ICARE study.

BACKGROUND: Few occupational studies have addressed head and neck cancer, and these studies have been predominantly conducted in men. Accordingly, our objective was to investigate the association between head and neck cancer and occupation in women. METHODS: ICARE, a French population-based case-control study, included 296 squamous cell carcinomas of the head and neck in women and 775 controls. Lifelong occupational history was collected. Odds ratios (ORs) and 95% confidence intervals (CI), adjusted for smoking, alcohol drinking and education level, were estimated for occupations and industries. RESULTS: An elevated OR was observed for working proprietors working for 10 years or more (OR = 3.83, 95% CI: 1.12-13.0) with a significant trend with duration of employment (P = 0.047). Elevated but non-significant ORs were observed for street vendors (OR = 3.76, 95% CI: 0.99-14.3, P for trend = 0.13), bakers (OR = 4.19, 95% CI: 0.63-27.9, P for trend = 0.06), and welders and flame cutters (OR = 2.18, 95% CI: 0.33-14.4, P for trend = 0.05). CONCLUSIONS: This exploratory study suggests a role of occupational exposures in the development of HN cancer in women. Further investigations of exposures to specific agents are needed.

An extensive epidemiological investigation of a kidney cancer cluster in a chemical plant: what have we learned?

OBJECTIVES: In 2003, a cluster of renal cell carcinoma (RCC) cases was reported among men working at a French chemical plant using a proprietary process to produce vitamin A. The 10 index cases yielded a standardised incidence ratio of 13.1 for 1994-2002. Nine of these 10 cases were diagnosed by a plant-specific abdominal ultrasonography screening programme that targeted exposure to an intermediate chemical, 4-chloro-1,1-dimethoxy-3-methyl-2-butene, commonly named 'chloracetal C5', suspected as the cause by some experts. Epidemiological investigations sought to examine the relations between occupational exposures and RCC. METHODS: A retrospective cohort mortality study and a nested case--control study were conducted. The cohort study included all workers who had been employed at the plant for at least 6 months between 1960 and 2003. The case--control study included an extensive search within the region for other kidney cancer cases among the cohort members. Industrial hygienists assessed occupational exposure. RESULTS: From 1968 to 2006, no significant excess mortality was observed for all causes of death or for all cancers. We found excess mortality for kidney cancer only among women. The nested case--control study showed a dose--response relation for cumulative exposure to chloracetal C5: the OR rose from 2.5 in the low-exposure category to 10.5 in the high-exposure group. Adjustment for screening attenuated this relation. CONCLUSIONS: The results of the case--control study were consistent with the positive results of in vivo genotoxic tests and suggest that chloracetal C5 can have a causal role in RCC.

Comparison of exposure assessment methods in a lung cancer case-control study: performance of a lifelong task-based questionnaire for asbestos and PAHs.

OBJECTIVE: To describe the performance of a lifelong task-based questionnaire (TBQ) in estimating exposures compared with other approaches in the context of a case-control study. METHODS: A sample of 93 subjects was randomly selected from a lung cancer case-control study corresponding to 497 jobs. For each job, exposure assessments for asbestos and polycyclic aromatic hydrocarbons (PAHs) were obtained by expertise (TBQ expertise) and by algorithm using the TBQ (TBQ algorithm) as well as by expert appraisals based on all available occupational data (REFERENCE expertise) considered to be the gold standard. Additionally, a Job Exposure Matrix (JEM)-based evaluation for asbestos was also obtained. On the 497 jobs, the various evaluations were contrasted using Cohen's κ coefficient of agreement. Additionally, on the total case-control population, the asbestos dose-response relationship based on the TBQ algorithm was compared with the JEM-based assessment. RESULTS: Regarding asbestos, the TBQ-exposure estimates agreed well with the REFERENCE estimate (TBQ expertise: level-weighted κ (lwk)=0.68; TBQ algorithm: lwk=0.61) but less so with the JEM estimate (TBQ expertise: lwk=0.31; TBQ algorithm: lwk=0.26). Regarding PAHs, the agreements between REFERENCE expertise and TBQ were less good (TBQ expertise: lwk=0.43; TBQ algorithm: lwk=0.36). In the case-control study analysis, the dose-response relationship between lung cancer and cumulative asbestos based on the JEM is less steep than with the TBQ-algorithm exposure assessment and statistically non-significant. CONCLUSIONS: Asbestos-exposure estimates based on the TBQ were consistent with the REFERENCE expertise and yielded a steeper dose-response relationship than the JEM. For PAHs, results were less clear.

Occupation and head and neck cancer risk in men: results from the ICARE study, a French population-based case-control study.

OBJECTIVE: To investigate the associations between occupations and head and neck (HN) cancer risk in men. METHODS: ICARE is a French population-based case-control study on HN cancer. Analyses included 1833 cases and 2747 controls. Complete occupational history was collected. Odds ratios (ORs) were estimated for occupations and industries ever held and according to duration of employment. RESULTS: Elevated ORs, increasing with duration of employment, were observed for several occupations, including cleaners (OR = 1.7; 95% confidence interval [CI], 1.0 to 2.8), launderers (OR = 6.8; CI, 1.3 to 34.4), firefighters (OR = 3.9; CI, 1.4 to 11.2), several agricultural occupations, welders (OR = 1.9; CI, 1.3 to 2.8), structural metal preparers and erectors (OR = 2.1; CI, 1.2 to 3.7), rubber workers (OR = 2.0; CI, 1.0 to 3.9), several construction occupations, and material-handling equipment operators (OR = 1.8; CI, 1.1 to 2.9). Analyses by industry corroborated these findings. CONCLUSIONS: These results confirmed the role of occupational exposures in HN cancer.

Occupational exposure to chlorinated and petroleum solvents and mycosis fungoides.

OBJECTIVE: To evaluate the potential association between occupational exposure to chlorinated and petroleum solvents and mycosis fungoides (MF). METHODS: A questionnaire on lifetime job history was administered to 100 patients diagnosed with MF and 2846 controls. Odds ratios (ORs) were calculated as the measure of the association between exposure to each specific solvent and MF. RESULTS: In the total sample and in men, cases and controls did not differ in relation to exposure to any of the solvents studied. In women, an association with MF was seen for the highest level of estimated exposure to perchloroethylene (OR = 11.38; 95% confidence interval: 1.04 to 124.85) and for exposure less than the median to kerosene/fuel/gasoil (OR = 8.53; 95% confidence interval: 1.11 to 65.62). CONCLUSIONS: These results do not provide conclusive evidence that exposure to solvents may increase risk of MF because they were not found in men.

Risk of lung cancer associated with occupational exposure to mineral wools: updating knowledge from a french population-based case-control study, the ICARE study.

OBJECTIVES: To assess the risk of lung cancer associated with exposure to mineral wools (MWs), while taking into account smoking, asbestos, and crystalline silica exposures. METHODS: The analyses were restricted to men (1350 cases and 1912 controls). Lifelong occupational history was collected. MWs and asbestos exposures were assessed, using task-exposure matrices and silica exposure, a job-exposure matrix. RESULTS: We observed consistent not-significant increased risks of lung cancer of the same order of magnitude among workers exposed to high levels of MWs (odds ratio, 1.4; 95% confidence interval: 0.9 to 2.2; for highest quartile of the Cumulative Exposure Index). CONCLUSIONS: These results do not allow to draw firm conclusion about a carcinogenic effect of MWs on the lung, but they cannot exclude it. Given the high number of potentially exposed workers, it will be necessary to replicate them in a future further removed from the asbestos ban.

Occupational exposure to ultraviolet radiation and risk of non-melanoma skin cancer in a multinational European study.

BACKGROUND: Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation. OBJECTIVES: We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia. METHODS: Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC. RESULTS: Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27-0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure. CONCLUSIONS: The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.

Occupational exposure to arsenic and risk of nonmelanoma skin cancer in a multinational European study.

Occupational studies show a high risk of lung cancer related to arsenic exposure by inhalation; however, only a few studies, and with conflicting results, previously examined a potential link between arsenic exposure at work and skin cancer. The aim of this study is to assess airborne arsenic exposures at the workplace and to quantify associations with nonmelanoma skin cancer (NMSC). The study sample consists of 618 incident cases of NMSC and 527 hospital-based controls aged 30-79 years from Hungary, Romania and Slovakia. Exposures were evaluated by local experts using occupational histories. Information on host factors and other exposures was collected and used to adjust the associations of interest using multivariable logistic regression. The lifetime prevalence of exposure to work-related arsenic is 23.9% for cases and 15.5% for controls. No significant association between arsenic exposure in the workplace and NMSC was detected, although an increased adjusted odd ratio was observed for participants with higher cumulative lifetime workplace exposure to arsenic in dust and fumes compared to referents [odds ratios (OR) = 1.94, 95% confidence interval (CI) = 0.76-4.95]. There is evidence for modification of the workplace arsenic-NMSC association by work-related sunlight exposure in women, with a markedly increased adjusted OR in the presence of workplace sunlight exposure (OR = 10.22, 95% CI = 2.48-42.07). Workplace coexposure to arsenic and sunlight may thus pose an increased risk of NMSC.

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.

Sensitivity analyses of exposure estimates from a quantitative job-exposure matrix (SYN-JEM) for use in community-based studies.

OBJECTIVES: We describe the elaboration and sensitivity analyses of a quantitative job-exposure matrix (SYN-JEM) for respirable crystalline silica (RCS). The aim was to gain insight into the robustness of the SYN-JEM RCS estimates based on critical decisions taken in the elaboration process. METHODS: SYN-JEM for RCS exposure consists of three axes (job, region, and year) based on estimates derived from a previously developed statistical model. To elaborate SYN-JEM, several decisions were taken: i.e. the application of (i) a single time trend; (ii) region-specific adjustments in RCS exposure; and (iii) a prior job-specific exposure level (by the semi-quantitative DOM-JEM), with an override of 0 mg/m(3) for jobs a priori defined as non-exposed. Furthermore, we assumed that exposure levels reached a ceiling in 1960 and remained constant prior to this date. We applied SYN-JEM to the occupational histories of subjects from a large international pooled community-based case-control study. Cumulative exposure levels derived with SYN-JEM were compared with those from alternative models, described by Pearson correlation ((Rp)) and differences in unit of exposure (mg/m(3)-year). Alternative models concerned changes in application of job- and region-specific estimates and exposure ceiling, and omitting the a priori exposure ranking. RESULTS: Cumulative exposure levels for the study subjects ranged from 0.01 to 60 mg/m(3)-years, with a median of 1.76 mg/m(3)-years. Exposure levels derived from SYN-JEM and alternative models were overall highly correlated (R(p) > 0.90), although somewhat lower when omitting the region estimate ((Rp) = 0.80) or not taking into account the assigned semi-quantitative exposure level (R(p) = 0.65). Modification of the time trend (i.e. exposure ceiling at 1950 or 1970, or assuming a decline before 1960) caused the largest changes in absolute exposure levels (26-33% difference), but without changing the relative ranking ((Rp) = 0.99). CONCLUSIONS: Exposure estimates derived from SYN-JEM appeared to be plausible compared with (historical) levels described in the literature. Decisions taken in the development of SYN-JEM did not critically change the cumulative exposure levels. The influence of region-specific estimates needs to be explored in future risk analyses.

Night work and breast cancer: a population-based case-control study in France (the CECILE study).

Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the role of night work in a large population-based case-control study carried out in France between 2005 and 2008. Lifetime occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and 1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR = 1.27 [95% confidence interval = 0.99-1.64]). Odds ratios were 1.35 [1.01-1.80] in women who worked on overnight shifts, 1.40 [1.01-1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01-2.03] in those who worked less than three nights per week on average. The odds ratio was 1.95 [1.13-3.35] in women employed in night work for >4 years before their first full-term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer, particularly in women who started working at night before first full-term pregnancy.