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ObjectiveTo 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.MethodsAnalyses 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.ResultsWelding 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 ConclusionOur findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.

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 logisticregressionmodelsadjustedfor 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 21 $yr 21 was 1.6 (95% CI, 1.2–2.1) and increased to 2.5 (95% CI, 1.8–3.4) for subjects exposed to more than 0.32 fibers$ml 21 $yr 21 . All ORs for silica exposure were around the null. CoexposuretoeitherasbestosandMWorasbestosandsilicaseemed toincreasethe risk ofpleuralmesothelioma. ORswere 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.

International audience; 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.

Background: The aim of this study was to compute attributable fractions (AF) to occupational factors in an area in North-Eastern France with high lung cancer rates and a past of mining and steel industry. Methods: A population-based case–control study among males aged 40–79 was conducted, including confirmed primary lung cancer cases from all hospitals of the study region. Controls were stratified by broad age-classes, district and socioeconomic classes. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative occupational exposure indices were obtained from the questionnaires. Attributable fractions were computed from multiple unconditional logistic regression models. Results: A total of 246 cases and 531 controls were included. The odds ratios (ORs) adjusted on cumulative smoking and family history of lung cancer increased significantly with the cumulative exposure indices to asbestos, polycyclic aromatic hydrocarbons and crystalline silica, and with exposure to diesel motor exhaust. The AF for occupational factors exceeded 50%, the most important contributor being crystalline silica and asbestos. Conclusion: These AFs are higher than most published figures. This can be because of the highly industrialised area or methods for exposure assessments. Occupational factors are important risk factors and should not be forgotten when defining high-risk lung cancer populations.

Occupation as a welder has been associated with a 25%-40% increase in lung cancer risk. This study aims to elucidate to what extent confounding by smoking and asbestos drives this association and to evaluate the role of welding-related exposures such as chromium. The study included 2,197 male incident lung cancer cases and 2,295 controls from Romania, Hungary, Poland, Russia, Slovakia, the Czech Republic, and the United Kingdom from 1998 to 2001. Information on risk factors was collected through face-to-face interviews. Experts assessed exposure to 70 agents, and risk estimates were adjusted for smoking and occupational exposures. Occupation as a welder/flame cutter (prevalence controls: 3.7%) was associated with an odds ratio of 1.36 (95% confidence interval (CI): 1.00, 1.86) after adjustment for smoking and occupational exposures including asbestos. An odds ratio of 1.18 (95% CI: 1.01, 1.38) was found for welding fumes (prevalence controls: 22.8%), increasing to 1.38 for more than 25 exposure years (95% CI: 1.09, 1.75). A duration-response association was also observed for mild steel welding without chromium exposure. In this population, occupational exposure to welding fumes accounted for approximately 4% of lung cancer cases, to which both stainless and mild steel welding contributed equally. Given that welding remains a common task for many workers, exposure to welding fumes represents an important risk factor for lung cancer. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

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.

Objectives Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries. Methods Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. ORs and 95% 95% CIs were estimated by unconditional logistic regression analyses and adjusted for several potential confounders. Results 293 case and 3198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilisers in forestry (OR=8.93; 95% CI 1.73 to 42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye colour. Conclusions Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased. The possible risk increase associated with exposure to chemical fertilisers should be reinvestigated in future studies.

Objectives Male breast cancer is a rare disease of largely unknown aetiology. In addition to genetic and hormone-related risk factors, a large number of environmental chemicals are suspected of playing a role in breast cancer. The identification of occupations or occupational exposures associated with an increased incidence of breast cancer in men may help to identify mammary carcinogens in the environment. Methods Occupational risk factors for male breast cancer were investigated in a multi-centre case-control study conducted in eight European countries which included 104 cases and 1901 controls. Lifetime work history was obtained during in-person interviews. Occupational exposures to endocrine disrupting chemicals (alkylphenolic compounds, phthalates, polychlorinated biphenyls and dioxins) were assessed on a case-by-case basis using expert judgement. Results Male breast cancer incidence was particularly increased in motor vehicle mechanics (OR 2.1, 95% CI 1.0 to 4.4) with a dose-effect relationship with duration of employment. It was also increased in paper makers and painters, forestry and logging workers, health and social workers, and furniture manufacture workers. The OR for exposure to alkylphenolic compounds above the median was 3.8 (95% CI 1.5 to 9.5). This association persisted after adjustment for occupational exposures to other environmental oestrogens. Conclusion These findings suggest that some environmental chemicals are possible mammary carcinogens. Petrol, organic petroleum solvents or polycyclic aromatic hydrocarbons are suspect because of the consistent elevated risk of male breast cancer observed in motor vehicle mechanics. Endocrine disruptors such as alkylphenolic compounds may play a role in breast cancer.

BACKGROUND: The role of crystalline silica dust as a possible cause of lung cancer has been controversial. Relatively few large community-based studies have been conducted to investigate the lung cancer risk from exposure to silica at low levels, taking into account potential confounding factors. METHODS: Detailed lifestyle and occupational information were collected from 2852 newly diagnosed cases of lung cancer and 3104 controls between 1998 and 2002 in 7 European countries. For each job held, local experts assessed the probability, intensity, and duration of silica exposure. RESULTS: Occupational exposure to crystalline silica was associated with an increased risk of lung cancer (odds ratio = 1.37; 95% confidence interval = 1.14-1.65). This risk was most apparent for the upper tertile of cumulative exposure (OR = 2.08; 95% CI = 1.49-2.90; P for trend

International audience; 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.

Occupational X-ray examination programs have been conducted in many countries to screen for occupational and nonoccupational respiratory diseases, resulting in widespread exposure to X-radiation. We conducted a multicentre case-control study of lung cancer in the Czech Republic, Hungary, Poland, Romania, Russia and Slovakia, including 2,589 cases and 2,859 controls enrolled during 1998-2002. We collected detailed information on occupational X-ray examinations, occupations and tobacco smoking. We calculated odds ratios of lung cancer via multiple logistic regression after adjustment for age, sex, center and tobacco smoking. Among controls 24.9% reported no X-ray examination, 62.9% reported 1-30 examinations and 12.2% reported more than 30 examinations. When we chose individuals with no examination as the reference group, the odds ratios of lung cancer were 1.21 (95% confidence interval [CI] 0.99-1.48), 1.33 (95% CI 1.08-1.64), 1.49 (95% CI 1.18-1.87), 1.52 (95% CI 1.17-1.99) and 2.15 (95% CI 1.50-3.08) for 1-10, 11-20, 21-30, 31-40 and more than 40 examinations, respectively (p-value of test for linear trend

Several industry-based cohort studies have addressed the risk of lung cancer following exposure to vinyl chloride, acrylonitrile and styrene, with inconsistent results and usually without smoking adjustment. These exposures are addressed here in a large case-control study with full adjustment for smoking. Almost 6000 subjects were included in a case-control study conducted in seven European countries. For each job they held, local experts assessed the exposure to a number of occupational agents, including vinyl chloride, acrylonitrile and styrene, on the basis of detailed occupational questionnaires. Information on tobacco consumption and other risk factors was also collected. The odds ratio (OR) for ever exposure to vinyl chloride was 1.05 (95% confidence interval, CI: 0.68-1.62) and a modest, non-significant increase in the risk of lung cancer was found in the highest exposed subgroup. The OR for ever exposure to acrylonitrile was 2.20 (95% CI: 1.11-4.36) with a positive dose-response relationship between estimated cumulative exposure and lung cancer risk. No association between exposure to styrene and lung cancer risk was found. In conclusion, we cannot exclude a weak association between occupational exposure to vinyl chloride and lung cancer risk. Exposure to acrylonitrile was associated in our study with risk of lung cancer. Exposure to styrene does not seem to increase lung cancer risk.

Background: Ultraviolet radiation has been suspected as a possible cause of ocular melanoma. Because this association is controversial, we examine the role of occupational exposure to ultraviolet radiation on the occurrence of this rare cancer. Material and methods: A population-based case–control study was conducted in 10 French administrative areas (departements). Cases were 50 patients with uveal melanoma diagnosed in 1995–1996. Controls were selected at random from electoral rolls, after stratification for age, gender, and area. Among 630 selected persons, 479 (76%) were interviewed. Data on personal characteristics, occupational history, and detailed information on each job held were obtained from face-to-face interviews using a standardized questionnaire. Estimates of occupational exposure to solar and artificial ultraviolet light were made using a job exposure matrix. Results: Results show elevated risks of ocular melanoma for people with light eye color, light skin color, and for subjects with several eye burns. The analysis based on the job exposure matrix showed a significantly increased risk of ocular melanoma in occupational groups exposed to artificial ultraviolet radiation, but not in outdoor occupational groups exposed to sunlight. An elevated risk of ocular melanoma was seen among welders (odds ratio = 7.3; 95% confidence interval = 2.6–20.1 for men), and a dose–response relationship with job duration was observed. The study also showed increased risk of ocular melanoma among male cooks, and among female metal workers and material handling operators. Conclusion: Following the present study, the existence of an excess risk of ocular melanoma in welders may now be considered as established. Exposure to ultraviolet light is a likely causal agent, but a possible role of other exposures in the welding processes should not be overlooked.

A case-control study on respiratory cancers was conducted in New Caledonia (South Pacific), where a high incidence of malignant pleural mesothelioma had been observed. The disease pattern suggested an environmental exposure to asbestos. The first results showed that, in some areas, tremolite asbestos derived from local outcroppings was used as whitewash (locally named "pö"). All cases diagnosed between 1993 and 1995 (including 15 pleural mesotheliomas, 228 lung cancers, and 23 laryngeal cancers) and 305 controls were included in the study. Detailed information on past or present use of the whitewash, residential history, smoking, diet, and occupation was collected. The risk of mesothelioma was strongly associated with the use of the whitewash (odds ratio (OR) = 40.9; 95% confidence interval (CI): 5.15, 325). All Melanesian cases had been exposed. Among Melanesian women, exposure to the whitewash was associated with an increased risk of lung cancer (OR = 4.89; 95% CI: 1.13, 21.2), and smokers exposed to po had an approximately ninefold risk (OR = 9.26; 95% CI: 1.72, 49.7) compared with women who never smoked and had never used the whitewash. In contrast, no association was noted between exposure to pö and lung cancer risk among Melanesian men, probably because of lower exposure levels. Among non-Melanesians, the numbers of exposed subjects were too small to assess the effect of exposure to po. There was no indication of elevated risks for the other cancer sites.

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 Cohen9s 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.

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.

We investigated the association between occupational exposure to endocrine-disrupting chemicals (EDC) and the risk of uveal melanoma using international data of a case-control study from nine European countries.After exclusion of proxy interviews, 280 cases and 3084 control subjects were included in the final analysis. Information on possible exposure to EDC was derived from 27 job-specific questionnaires (JSQ), which solicited detailed questions on occupational tasks. Relative risk estimates were based on the JSQ and potential exposure to a group of endocrine-disrupting agents. We constructed several exposure scores, taking into account intensity of exposure, use of personal protective equipment, and exposure duration. We calculated unconditional logistic regression analyses, adjusting for country, age, sex, eye color and a history of ocular damage due to intense ultraviolet (UV) exposure.The overall exposure prevalence to EDC was low reaching a maximum of 11% for heavy metals with endocrine-disrupting properties. Although working in some industries was associated with increased melanoma risk [such as dry cleaning: odds ratio (OR) 6.15, 95% confidence interval (95% CI) 2.0-18.96 and working in the glass manufacturing industry: OR 3.49, 95% CI 1.10-11.10], agent-specific risks were not elevated. The strongest possible risk increase was observed for organic solvents with endocrine-disrupting properties (OR 1.31, 95% CI 0.78-2.21). Calculation of exposure scores did not indicate consistently elevated results with higher score values. Sensitivity analyses did not alter these results.Occupational exposure to EDC was not associated with an increased risk for uveal melanoma.

In New Zealand, there is a need for a comprehensive and accessible database with national occupational exposure information, such as a general population job-exposure matrix (GPJEM). However, few New Zealand-specific exposure data exist that could be used to construct such a GPJEM. Here, we present the methods used to develop a GPJEM for New Zealand (NZJEM), by combining GPJEMs from other countries with New Zealand-specific exposure information, using wood dust as an example to illustrate this process. The assessments of GPJEMs from other countries were made available to a New Zealand expert in occupational wood dust exposure, who then provided a preliminary NZJEM assessment (including the percentage exposed and the level of exposure for each occupation). Where possible, this assessment was based on New Zealand exposure measurements. In the next step, information from a nationwide workplace exposure survey of 3000 members of the New Zealand workforce was used to finalize the NZJEM assessments. The final NZJEM listed 104 of the 956 New Zealand occupational codes as exposed to wood dust. The percentage of workers exposed within an occupation ranged from 5% (e.g. boiler attendants) to 100% (e.g. cabinet makers). The level of exposure ranged from 0.05 mg m(-3) (e.g. electricians) to 3 mg m(-3) (e.g. carpenters). Of these assessments, 23% were mainly based on New Zealand exposure data, 37% on overseas GPJEMs and exposure data, and for 40% the national survey data served as the main source of information for the expert assessment. Combining the NZJEM assessments with national employment statistics indicated that 5.6% of the New Zealand workforce is occupationally exposed to wood dust, corresponding to a total of 97 000 workers (86% male and 14% female). Construction-related occupations included the largest number of exposed workers.

Objectives In order to estimate the exposure-response relation of respirable quartz and lung cancer risk, we developed a quantitative time/job/region specific job-exposure matrix (JEM) based on statistical modelling of historical exposure data. We compared the performance of this quantitative JEM (SYN-JEM) with an already available semi-quantitative general population JEM (DOM-JEM) within a study of pooled community-based lung cancer case-control studies (SYNERGY). Methods Detailed lifetime occupational and smoking history was available for 13 259 cases and 16 232 controls from 11 case-control studies from 12 European countries and Canada. Occupational histories were linked with SYN-JEM and DOM-JEM to derive estimates of cumulative exposure. ORs for lung cancer were estimated using unconditional logistic regression adjusted for age, gender, study, cigarette pack-years, time-since-quitting smoking, and ever occupational exposure to five other known lung carcinogens. Results Exposure to respirable quartz was associated with a monotonic increase in risk of lung cancer. Cumulative exposure estimates based on the quantitative SYN-JEM ranged from 0.005 to 104 mg/m3-years. Quartiles of cumulative exposure (categorised using the exposure distribution among exposed controls) showed significant elevated risks ranging from 1.16 to 1.40. SYN-JEM did not perform better than the ordinal DOM-JEM which provided similar ORs. Conclusions We found a positive exposure-response association between occupational exposure to respirable quartz and lung cancer in a large pooled community-based case-control study. A semi-quantitative approach showed similar results as the quantitative exposure assessment approach except that with the latter risk can be expressed in terms of mg/m3 quartz years, which would facilitate quantitative risk-assessment.

Objectives Quantitative exposure assessment in a multinational pooled-analysis of community-based lung cancer case-control studies can be reached via exposure modelling of occupational exposure measurements. We describe a modelling framework for respirable quartz exposure to create a quantitative job-exposure matrix (JEM). Methods Personal measurements of respirable quartz exposure from Europe and Canada were obtained for exposure modelling. A mixed-effects model was used, with region and job titles (ISCO 1968 coding) as random-effect terms. The fixed-effect terms included time period (years), measurement strategy (representative or worst-case), sampler device (categorical), sampling duration (minutes) and a-priori intensity expert ratings for each job from an independently developed JEM (ordinal 0–2). Results 30 393 respirable quartz exposure measurements covering the time period from 1976 to 2009 were used for modelling, showing an overall time trend of -7% per year. An effect of region was found with higher exposures in Canada and the UK and lower exposure levels in Northern and Southern Europe. The other fixed-effect variables influenced exposures in line with a-priori expectation, for example, estimates for worst-case scenarios were higher than for representative situations, samplers with PUF foam under sampled respirable quartz as compared to sampling with filters, and sampling duration was negatively associated with exposure level. Conclusions The modelling exercise showed that quantitative data can be used to derive a quantitative JEM. The presented model will allow us to predict time, job, and region specific exposure levels of respirable quartz. These predictions will be used in the SYNERGY study, an ongoing international pooled community-based case-control study on lung cancer.

Udgivelsesdato: 2009-Nov-30 The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure to wood dust, using capillary electrophoresis single-strand conformation polymorphism analysis and direct sequencing. A significant association between wood-dust exposure and adenocarcinoma histology was observed [adjusted odds ratio (OR) 12.6, 95% confidence interval (CI), 5.0-31.6]. TP53 mutations occurred in all histologies, with an overall frequency of 77%. TP53 mutation positive status was most common in adenocarcinoma (OR 2.0, 95% CI, 1.1-3.7; compared with squamous cell carcinoma), and mutation positivity showed an overall, nonsignificant association with wood-dust exposure (OR 1.6, 95% CI, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (>/=24 years, OR 5.1, 95% CI, 1.5-17.1), average level (>2 mg/m(3); OR 3.6, 95% CI, 1.2-10.8) and cumulative level (>/=30 mg/m(3) x years; OR 3.5, 95% CI, 1.2-10.7) of wood-dust exposure; adjustment for formaldehyde affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p = 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.

Objectives: To assess the mortality of a cohort of workers in a synthetic textile spinning plant and to evaluate the relationship between mortality from lung, liver and bladder cancer and the processes or the products used. Methods: The study population consisted of male workers present for at least 6 months in the plant from 1968 to 1984. The cohort was followed until 1999. Vital status and the causes of death were determined by consulting national registries. The population of the Franche-Comte region was used for comparison. In total, 17 groups of exposure were assessed by the industrial hygienist, based on the consensus of an expert group that determined the exposure levels of each job to selected occupational hazards. Each worker was assigned to one or several groups, according to his occupational history. Confounding factors could not be assessed. Standardised mortality ratios (SMR) and 95% bilateral confidence intervals were calculated based on an assumed Poisson distribution of the number of cases to compare the plant mortality and the population mortality. Internal analyses were performed with Cox models in order to assess the risks of death related to the various exposures. Results: In the whole cohort, mortality from all malignant neoplasms was lower than expected, but this was not significant. All the estimated SMRs were lower than or close to 1. The “hot -line fitters” (RR = 2.13; n = 9; 1.06 to 4.29) and the “fibre-drawing workers” (RR = 1.83; n = 20;1.09 to 3.07) experienced a statistically significant excess in mortality from lung cancer. A slightly elevated but not significant risk of death related to lung cancer (RR = 1.5; n = 41; 0.8 to 2.7) was observed in the groups with the highest exposure to mineral fibres. A statistically significant increase in cancer deaths was observed for workers with high exposure to dust (higher intensity: RR = 1.42; n = 79; 1.06 to 1.89). Conclusion: Some findings, mainly of lung cancer, justify further exploration in other plants in this industry

Objectives: To investigate the contribution of occupational exposure to asbestos and man-made vitreous fibres (MMVF) to lung cancer in high-risk populations in Europe. Methods: A multicentre case-control study was conducted in six Central and Eastern European countries and the UK, during the period 1998–2002. Comprehensive occupational and sociodemographic information was collected from 2205 newly diagnosed male lung cancer cases and 2305 frequency matched controls. Odds ratios (OR) of lung cancer were calculated after adjusting for other relevant occupational exposures and tobacco smoking. Results: The OR for asbestos exposure was 0.92 (95% CI 0.73 to 1.15) in Central and Eastern Europe and 1.85 (95% CI 1.07 to 3.21) in the UK. Similar ORs were found for exposure to amphibole asbestos. The OR for MMVF exposure was 1.23 (95% CI 0.88 to 1.71) with no evidence of heterogeneity by country. No synergistic effect either between asbestos and MMVF or between any of them and smoking was found. Conclusion: In this large community-based study occupational exposure to asbestos and MMVF does not appear to contribute to the lung cancer burden in men in Central and Eastern Europe. In contrast, in the UK the authors found an increased risk of lung cancer following exposure to asbestos. Differences in fibre type and circumstances of exposure may explain these results.

A method for a semi-quantitative retrospective assessment of exposure to trichloroethylene (TCE) was implemented for a case-control study conducted in the Arve valley (France), an area with a widely developed screw-cutting industry, where teams of occupational physicians have collected a large quantity of well-documented measurements. A task-exposure matrix was developed to link the main working circumstances in a screw-cutting workshop to corresponding TCE-exposure levels: a 'basic level' was assigned to each task, standing for usual working procedures; exposure circumstances, such as duration or distance from the TCE source, were introduced as corrective factors. In parallel, a detailed occupational questionnaire was designed, setting subjects' descriptions of their successive jobs and working circumstances against levels assessed in the matrix. Possible exposure to TCE, plus some other occupational compounds (other solvents, oils, some metals, asbestos, welding fumes and ionizing radiations), were assessed for any job in all job histories. An average level of exposure to TCE, related to an 8 h usual working day, was attributed to each job period in turn, which was then categorized into six classes: 0; 1-35; 35-50; 50-75; 75-100; and100 p.p.m. A total of 402 study subjects described their occupational life (average 3.7 jobs/subject, from 1924 to 2003). About 19% of the 1486 job periods described were assessed as being exposed to TCE; of these, 72.2% involved levels35 p.p.m., 13.2% involved levels50 p.p.m. and 5.4% above the French occupational exposure limit of 75 p.p.m. (TWA 8 h). A total of 41 job periods included exposure with peaks. Compared with levels encountered in other studies, the more severely exposed part of our study population seemed more exposed than most other populations previously studied, owing to vapor degreasing practices.

To test the effect of the exposure to trichloroethylene (TCE) on renal cell cancer (RCC) risk, a case-control study was performed in the Arve Valley (France), a geographic area with a high frequency and a high degree of such exposure. Cases and controls were selected from various sources: local general practitioners and urologists practicing in the area and physicians (urologists and oncologists) from other hospitals of the region who might treat patients from this area. Blinded telephone interviews with cases and controls were administered by a single trained interviewer using occupational and medical questionnaires. The analysis concerned 86 cases and 316 controls matched for age and gender. Three approaches were developed to assess the link between TCE exposure and RCC: exposure to TCE for at least one job period (minimum 1 year), cumulative dose (number of p.p.m. of TCE per job period multiplied by the number of years in the job period) and the effect of exposure to peaks. Multivariate analysis was performed taking into account potential confounding factors. Allowing for tobacco smoking and Body Mass Index, a significantly 2-fold increased risk was identified for high cumulative doses: odds ratio (OR)=2.16 (1.02-4.60). A dose-response relationship was identified, as was a peak effect; the adjusted OR for highest class of exposure-plus-peak being 2.73 (1.06-7.07). After adjusting for exposure to cutting fluids the ORs, although still high, were not significant because of lack of power. This study suggests an association between exposures to high levels of TCE and increased risk of RCC. Further epidemiological studies are necessary to analyze the effect of lower levels of exposure.

International audience; OBJECTIVE: Uveal melanoma is a rare disease with poor prognosis and largely unknown etiology. We studied potential occupational risk factors. METHODS: A population based case-control study was undertaken during 1995-1997 in nine European countries using population and colon cancer controls with personal interviews. Occupational exposure to sunlight and artificial UV radiation was assessed with a job exposure matrix. In total, 320 uveal melanoma cases were eligible at pathology review, and 292 cases were interviewed, participation 91%. Out of 3357 population controls, 2062 were interviewed, 61%, and out of 1272 cancer controls 1094 were interviewed, 86%. RESULTS: Using population controls, occupational exposure to sunlight was not associated with an increased risk (RR=1.24, 95% CI=0.88-1.74), while an excess risk found with use of colon cancer controls was attributed to confounding factors. An excess risk in welders was restricted to the French part of the data. Cooks, RR=2.40; cleaners, RR 2.15; and laundry workers, RR=3.14, were at increased risk of uveal melanoma. CONCLUSION: Our study does overall not support an association between occupational sunlight exposure and risk of uveal melanoma. The finding of an excess risk of eye melanoma in cooks in several European countries is intriguing.

BACKGROUND: In a multicenter case-control study of lung cancer in central and eastern Europe and in Liverpool, exposure to occupational agents was assessed by teams of local experts. We performed an interteam agreement study to estimate the levels of exposure misclassification and the expected attenuation of the risk estimate. METHODS: Eight teams of experts and a reference rater assessed exposure to 70 putative lung carcinogens for 19 jobs. Agreement among teams was calculated through Cohen's kappa, sensitivity, and specificity. RESULTS: Each team showed an overall fair to good agreement with the reference (kappa between 0.53 and 0.64). The agreement among teams in the presence of exposure was excellent for 9 agents, fair to good for 16, and poor for 29. For all agents the specificity was high (average 0.94), although sensitivity varied considerably. CONCLUSIONS: This study of expert exposure assessment showed a small range in reliability among teams of experts, but large differences among agents. This paper presents the range in levels of misclassification that can be expected using experts for assessing occupational exposure to different agents, and the attenuation of the odds ratio that can be expected to result from this misclassification.

Introduction Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries. Methods Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. ORs and 95% CIs were estimated by unconditional logistic regression analyses and adjusted for several potential confounders. Results 293 case and 3198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilisers in forestry (OR 8.93; 95% CI 1.73 to 42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye colour. Conclusion Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures. The possible risk increase associated with exposure to chemical fertilisers should be reinvestigated in future studies.

Objectives This work aims at assessing the risk of lung cancer associated with mineral wools (MW) currently used as a substitute for asbestos. They are suspected of increasing the risk of lung cancer because of their structure close to asbestos. Methods ICARE is a large multicentre population-based case-control study conducted between 2001 and 2006 in 10 French departments with a general cancer registry. ICARE includes 2926 incident lung cancer cases and 3555 controls with 78% of men. The subjects9 exposure to MW was first determined using a Job-Exposure Matrix (JEM) specific for MW. Then, individual exposure was assessed with an algorithm using specific questions on exposing tasks. We used unconditional logistic regression adjusted for age, department, number of job periods, lifelong cigarette smoking and exposure to asbestos (also assessed by a JEM and an algorithm). Results Analyses were conducted among men (2301 cases, 2780 controls) and concerned 27191 jobs. In the first analyses, we find significant associations between the risk of lung cancer and exposure to MW assessed with the JEM. They became non non-significant and close to 1 when adjusting for exposure to asbestos. In contrast, a significant dose-response relation was found between exposure to asbestos and the risk of lung cancer, even when adjusted for exposure to MW. Conclusions These results need to be completed with the exposure assessment from the algorithm. This algorithm would help us disentangle MW and asbestos exposure, which are closely related because of similar exposing jobs. Both results will be presented.

Objectives We estimated the lung cancer risk following occupational exposure to carbon black while adjusting for smoking, and explored the effect of time-windows of carbon black exposure since recent studies have hypothesised that recent exposure is the most important time-window for carbon black exposure. Methods The multicenter case-control study on lung cancer was conducted from 1998 to 2002 in seven European countries; 2861 cases and 2936 controls were recruited. Occupational and socio-demographic information was collected through interviews. Industrial hygiene experts in each country evaluated exposure to 70 occupational agents, including carbon black. Unconditional logistic regression models were applied to calculate ORs and 95% CIs adjusting for centre, sex, other occupational exposures and tobacco smoking. Results The OR for ever exposure to carbon black was 1.64 (95% CI 1.09 to 2.46). We observed a significant dose-response trend for maximum intensity (p-value, 0.02) and average intensity (p-value, 0.03). The OR for the highest exposure category of cumulative exposure in the last 15-years was OR 3.32 (95% CI 1.22 to 9.03). Conclusions The results show an association between occupational exposure to carbon black and lung cancer risk, and a significant dose-response relationship with increasing intensity. The most recent 15 years appear to be the most relevant time of exposure.