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Objectives: The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints., Methods: Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk., Results: SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates., Conclusion: The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) ( P trend  = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure ( P trend  < 0.001) and a decreasing trend with longer time since last exposure ( P trend  = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Background: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents., Objectives: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking., Methods: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI)., Results: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8)., Discussion: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Exposure to polycyclic aromatic hydrocarbons (PAH) occurs widely in occupational settings. We investigated the association between occupational exposure to PAH and lung cancer risk and joint effects with smoking within the SYNERGY project., Methods: We pooled 14 case-control studies with information on lifetime occupational and smoking histories conducted between 1985 and 2010 in Europe and Canada. Exposure to benzo[a]pyrene (BaP) was used as a proxy of PAH and estimated from a quantitative general population job-exposure matrix. Multivariable unconditional logistic regression models, adjusted for smoking and exposure to other occupational lung carcinogens, estimated ORs, and 95% confidence intervals (CI)., Results: We included 16,901 lung cancer cases and 20,965 frequency-matched controls. Adjusted OR for PAH exposure (ever) was 1.08 (CI, 1.02-1.15) in men and 1.20 (CI, 1.04-1.38) in women. When stratified by smoking status and histologic subtype, the OR for cumulative exposure ≥0.24 BaP μg/m3-years in men was higher in never smokers overall [1.31 (CI, 0.98-1.75)], for small cell [2.53 (CI, 1.28-4.99)] and squamous cell cancers [1.33 (CI, 0.80-2.21)]. Joint effects between PAH and smoking were observed. Restricting analysis to the most recent studies showed no increased risk., Conclusions: Elevated lung cancer risk associated with PAH exposure was observed in both sexes, particularly for small cell and squamous cell cancers, after accounting for cigarette smoking and exposure to other occupational lung carcinogens., Impact: The lack of association between PAH and lung cancer in more recent studies merits further research under today's exposure conditions and worker protection measures., (©2022 The Authors; Published by the American Association for Cancer Research.)

Objectives: We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer., Methods: In 13 case-control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands - each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman's Standard International Occupational Prestige Scale) were affected by adjustment for the job indices., Results: In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56-1.93), PSI 1.33 (95% CI 1.17-1.51)] and women [PHI 1.62 (95% CI 1.24-2.11), PSI 1.31 (95% CI 1.09-1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32-1.58) to 1.30 (95% CI 1.17-1.45)], but not PSI., Conclusions: Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.

Objectives: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project., Methods: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens., Results: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0)., Conclusions: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes. Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations. Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m 3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined. Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype. Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks. Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed. Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated ( P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated ( P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes. Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.

Background: Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies., Methods: We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends., Results: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women., Conclusions: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.).

Objectives: The aim of this study was to explore lung cancer risk among firefighters, with adjustment for smoking., Methods: We used pooled information from the SYNERGY project including 14 case-control studies conducted in Europe, Canada, New Zealand, and China, with lifetime work histories and smoking habits for 14,748 cases of lung cancer and 17,543 controls. We estimated odds ratios by unconditional logistic regression with adjustment for smoking and having ever been employed in a job known to present an excess risk of lung cancer., Results: There was no increased lung cancer risk overall or by specific cell type among firefighters (n = 190), neither before nor after smoking adjustment. We observed no significant exposure-response relationship in terms of work duration., Conclusions: We found no evidence of an excess lung cancer risk related to occupational exposure as a firefighter.

Background: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case-control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory., Methods: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman's Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results., Results: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13-1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32-1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88-1.46 for high to low, and 1.24; 95 % CI 1.08-1.41 for medium to low trajectories., Conclusions: Our results indicate that occupational prestige is independently associated with lung cancer among men.

Objectives: Working in mines and quarries has been associated with an elevated lung cancer risk but with inconsistent results for coal miners. This study aimed to estimate the smoking-adjusted lung cancer risk among coal miners and compare the risk pattern with lung cancer risks among ore miners and quarrymen., Methods: We estimated lung cancer risks of coal and ore miners and quarrymen among 14 251 lung cancer cases and 17 267 controls from the SYNERGY pooled case-control study, controlling for smoking and employment in other at-risk occupations., Results: Ever working as miner or quarryman (690 cases, 436 controls) was associated with an elevated odds ratio (OR) of 1.55 [95% confidence interval (95% CI) 1.34-1.79] for lung cancer. Ore miners (53 cases, 24 controls) had a higher OR (2.34, 95% CI 1.36-4.03) than quarrymen (67 cases, 39 controls; OR 1.92, 95% CI 1.21-3.05) and coal miners (442 cases, 297 controls; OR 1.40, 95% CI 1.18-1.67), but CI overlapped. We did not observe trends by duration of exposure or time since last exposure., Conclusions: This pooled analysis of population-based studies demonstrated an excess lung cancer risk among miners and quarrymen that remained increased after adjustment for detailed smoking history and working in other at-risk occupations. The increase in risk among coal miners were less pronounced than for ore miners or quarrymen.

Objectives: To investigate the risk of lung cancer among cooks, while controlling for smoking habits., Methods: We used data from the SYNERGY project including pooled information on lifetime work histories and smoking habits from 16 case-control studies conducted in Europe, Canada, New Zealand, and China., Results: Before adjustment for smoking, we observed an increased risk of lung cancer in male cooks, but not in female cooks. After adjusting, there was no increased risk and no significant exposure-response relationship. Nevertheless, subgroup analyses highlighted some possible excess risks of squamous cell carcinoma and small cell carcinoma in female cooks., Conclusions: There is evidence that lung cancer risks among cooks may be confounded by smoking. After adjustment, cooks did not experience an increased risk of lung cancer overall. The subgroup analyses showing some excess risks among female cooks require cautious interpretation.

Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos., (© 2014 UICC.)

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer.

Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies.

Introduction: Some studies have suggested increased lung cancer risks among bakers, however the results overall were inconsistent. The authors studied lung cancer risks among bakers and baking-related occupations in the SYNERGY pooled case-control database from 16 countries., Methods: Occupation in a baking-related job was identified from the subjects' job histories. ORs adjusted for log(age), study centre, smoking behaviour and ever employment in a job with known exposure to occupational lung carcinogens were calculated by unconditional logistic regression. Findings were stratified by sex, histological subtype of lung cancer and smoking status., Results: 19 366 cases (15 606 men) and 23 670 control subjects (18 528 men) were included. 473 cases (415 men, 58 women) and 501 controls (437 men, 64 women) had ever worked in baking or a related job. We did not observe an increased risk for men in baking (OR 1.01; 95% CI 0.86 to 1.18). No linear trends were observed for duration of employment. Some results suggested increased lung cancer risks for women, for example, for working as a baker for >30 years and in never-smokers, but after exclusion of one study these increased risks disappeared., Discussion: The findings from this study do not suggest increased lung cancer risks in baking-related professions.

Introduction: In a previous analysis of a case-control study of testicular cancer nested in a cohort of automobile workers, we observed an increased risk for testicular cancer among workers who had ever been involved in occupational metal-cutting tasks. We investigated whether this risk increase was due to exposure to metal-working fluids (MWF)., Methods: Occupational exposure to MWF was assessed in detail using a job-specific questionnaire for metal-cutting work. We calculated ORs and associated 95% CIs individually matched for age (±2 years) and adjusted for a history of cryptorchidism by conditional logistic regression., Results: The prevalence of exposure to MWF was 39.8% among cases and 40.1% among controls. For total germ cell tumours and seminomas we did not observe risk increases for metal-cutting tasks or occupational exposure to MWF (OR 0.95; 95% CI 0.69 to 1.32 and OR 0.88; 95% CI 0.58 to 1.35, respectively). However, dermal exposure to oil-based MWF was associated with an increased risk for non-seminomatous testicular cancer. Dermal exposure to oil-based MWF for more than 5000 h showed particularly high risk estimates (OR 4.72; 95% CI 1.48 to 15.09)., Discussion: Long-term dermal exposure to oil-based MWF was a risk factor for the development of non-seminomatous testicular germ cell cancer. Possible measures to reduce exposure include the introduction of engineering control measures such as venting or enclosing of machines, and enforcing the use of personal protective equipment during metal cutting.

Background: Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk, while exposure to microbial components (eg, endotoxin) has been associated with a decreased risk. To date there has not been a comprehensive evaluation of the possible association between occupational organic dust exposure (and its specific constituents) and lung cancer risk in the general population., Methods: The SYNERGY project has pooled information on lifetime working and smoking from 13 300 lung cancer cases and 16 273 controls from 11 case-control studies conducted in Europe and Canada. A newly developed general population job-exposure matrix (assigning no, low or high exposure to organic dust, endotoxin, and contact with animals or fresh animal products) was applied to determine level of exposure. ORs for lung cancer were estimated by logistic regression, adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk., Results: Occupational organic dust exposure was associated with increased lung cancer risk. The second to the fourth quartile of cumulative exposure showed significant risk estimates ranging from 1.12 to 1.24 in a dose-dependent manner (p<0.001). This association remained in the highest quartile after restricting analyses to subjects without chronic obstructive pulmonary disease or asthma. No association was observed between lung cancer and exposure to endotoxin or contact with animals or animal products., Conclusion: Occupational exposure to organic dust was associated with increased lung cancer risk in this large pooled case-control study.

Objectives: A system for retrospective occupational exposure assessment combining the efficiency of a job exposure matrix (JEM) and the precision of a subsequent individual expert exposure assessment (IEEA) was developed. All steps of the exposure assessment were performed by an interdisciplinary expert panel in the context of a case-control study on male germ cell cancer nested in the car manufacturing industries., Methods: An industry-specific JEM was developed and automatic exposure estimation was performed based on this JEM. A subsample of exposure ratings was done by IEEA to identify determinants of disagreement between the JEM and the individual review. Possible determinants were analyzed by calculating odds ratios (ORs) of disagreement between ratings with regard to different dimensions (e.g. high versus low intensity of exposure). Disagreement in ≥20% of the sampled exposure ratings with a statistically significant OR was chosen as a threshold for inclusion of the exposure ratings into a final IEEA., Results: The most important determinants of disagreement between JEM and individual review were working outside of the production line (disagreement 80%), low probability of exposure (disagreement 25%), and exposure depending on specific activities like usage of specific lacquers (disagreement 32%) for jobs within the production line. These determinants were the selection criteria of exposure ratings for the subsequent final IEEA., Conclusions: Combining a JEM and a subsequent final IEEA for a selected subset of exposure ratings is a feasible and labor-saving approach for exposure assessment in large occupational epidemiological studies.

Rationale: Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure-response relationships., Objectives: Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders., Methods: The SYNERGY project pooled information on lifetime work histories and tobacco smoking from 13,304 cases and 16,282 controls from 11 case-control studies conducted in Europe and Canada. A general population job exposure matrix based on ISCO-68 occupational codes, assigning no, low, or high exposure to diesel motor exhaust, was applied to determine level of exposure., Measurements and Main Results: Odds ratios of lung cancer and 95% confidence intervals were estimated by unconditional logistic regression, adjusted for age, sex, study, ever-employment in an occupation with established lung cancer risk, cigarette pack-years, and time-since-quitting smoking. Cumulative diesel exposure was associated with an increased lung cancer risk highest quartile versus unexposed (odds ratio 1.31; 95% confidence interval, 1.19-1.43), and a significant exposure-response relationship (P value < 0.01). Corresponding effect estimates were similar in workers never employed in occupations with established lung cancer risk, and in women and never-smokers, although not statistically significant., Conclusions: Our results show a consistent association between occupational exposure to diesel motor exhaust and increased risk of lung cancer. This association is unlikely explained by bias or confounding, which we addressed by adjusted models and subgroup analyses.

Aims: To assess the cumulative effect of asbestos on lung cancer risk where the exposure is assessed by an expert rating., Methods: 1678 male cases and controls were enrolled in a population based matched case-control study, focused on occupational risk factors, carried out in West Germany. The exposure to asbestos was computed as lifelong working hours. For a validation subsample of 164 matched pairs from this study the intensity of asbestos exposure was further assessed by a panel of experts in order to obtain an estimate of the cumulative exposure on a time by intensity scale (fibreyears). The information on duration of asbestos exposure in the original study was combined with the fibreyears following the two phase case control study paradigm., Results: The number of exposed subjects in the validation subsample was 75 cases and 71 controls. The percentage of subjects with a cumulative exposure < or =1, 1 to < or =10, and >10 fibreyears was 16%, 15%, and 15% for the cases and 18%, 16%, and 9% respectively for the controls. The smoking adjusted odds ratios for the fibreyears based on an unconditional logistic regression were 0.81, 1.02, and 1.60 respectively with increasing exposure categories (not significant). The coefficient (beta) for a log transformed trend was 1.156. Applying the two phase paradigm, these odds ratios became 0.86, 1.33, and 1.94; the latter reached significance and the beta coefficient was 1.178., Conclusions: The two phase paradigm allowed us to obtain a more precise estimate of the effect of asbestos on lung cancer. Results are consistent with a doubling of the lung cancer risk with 25 fibreyears asbestos exposure.

Background: Numerous studies have been carried out to evaluate the association between lung cancer and occupational asbestos exposure. However, the effects of timing of exposure have not been analyzed thoroughly., Methods: Two German case-control studies with data on occupational asbestos exposure histories have been pooled. Duration of work in potentially asbestos exposed jobs and two derived weighted exposure measures are analyzed together with time since last exposure. A spline function is used to model the effect of time since exposure., Results: The odds ratios (OR) and corresponding 95% confidence intervals were 1.8 (1.2, 2.7) and 2.4 (1.7, 3.4) for subjects having worked for 3 to 7 years and 8 or more years, respectively, in a job with potential asbestos exposure compared to never-exposed. Based on an evaluation of time since last exposure, the OR decreased significantly to about one-half after more than 20 years since exposure ceased. Using a spline function, applied to workers' complete exposure histories, the effect of an increment of exposure is greatest 10-15 years after that exposure was received., Conclusions: In contrast to previous indications, the risk of lung cancer increases soon after asbestos exposure, with its maximum effect from 10 to 15 years after the exposure was received.

We conducted a case-control study in 12 European study centers to evaluate the role of occupational risk factors among nonsmokers. We obtained detailed occupational histories from 650 nonsmoking cases (509 females/141 males) and 1,542 nonsmoking controls (1,011 females/531 males). On the basis of an a priori definition of occupations and industries that are known (list A) or suspected (list B) to be associated with lung carcinogenesis, we calculated odds ratios (ORs) for these occupations, using unconditional logistic regression models and adjusting for sex, age, and center effects. Among nonsmoking men, an excess relative risk was observed among those who had worked in list-A occupations [OR = 1.52; 95% confidence interval (C) = 0.78-2.97] but not in list-B occupations (OR = 1.05; 95%), CI = 0.60-1.83). Among nonsmoking women, there was an elevation of risk for list-A occupations (OR = 1.50; 95% CI = 0.49-4.53), although this estimate was imprecise, given that less than 1% of cases and controls were exposed. Exposure to list-B occupations was associated with an increase in relative risk (OR = 1.69; 95% CI = 1.09-2.63) in females, but not in males. Women who had been laundry workers or dry cleaners had an OR of 1.83 (95% CI = 0.98-3.40). Our findings confirm that certain occupational exposures are associated with an increased risk for lung cancer among both female and male nonsmokers; however, knowledge on occupational lung carcinogens is biased toward agents to which mainly men are exposed.

Background: To investigate the association between lung cancer and occupational exposure to man-made vitreous fibers (MMVF), a pooled analysis of two case-control studies was conducted in the years 1988-1994., Methods: The case series consisted of 3498 males who were histologically or cytologically verified primary lung cancer cases. 3541 male population controls were drawn at random from the general population and matched to cases by sex, age, and place of residence. To examine the relationship between MMVF and lung cancer we asked all study subjects who worked for at least 6 months as construction and installation workers whether they ever installed or removed insulations and what kind of insulation material they used., Results: Some 304 (8.7%) cases and 170 (4.8%) controls reported to have insulated with glass wool or mineral wool mats. Coded as ever/never exposed, the odds ratio was 1.48 (95% CI: 1.17-1.88), adjusted for smoking and asbestos. To be sure to exclude any confounding effect of asbestos, we tried to identify those cases and controls who insulated with glass wool or mineral wool mats only and never reported any asbestos exposure. For this group we calculated an odds ratio of 1.56 (95% CI: 0.92-2.65), after adjustment for smoking. An elevated risk was also estimated on the basis of an expert rating which was done for a subgroup of cases and controls. Ever exposure to MMVF (but not to asbestos) in this subgroup yielded an odds ratio of 1.30 (95% CI: 0.82-2.07)., Conclusions: Our study provides some indication for an excess risk of man-made vitreous fibers. This result also persists after adjustment for smoking and asbestos., (Copyright 2000 Wiley-Liss, Inc.)

Occupational exposures such as crystalline silica, diesel engine exhaust, polycyclic aromatic hydrocarbons, and man-made mineral fibers are strongly suspected to increase lung cancer risk. Two case-control studies in Germany conducted between 1988 and 1996 were pooled for a joint analysis. A total of 3,498 male cases and 3,541 male population controls, frequency matched for age and region, were included in the study. The lifelong history of all jobs and industries was coded and occupational exposures were evaluated by expert rating. Odds ratios, crude and adjusted for smoking and asbestos exposure, were calculated by conditional logistic regression. Job-related evaluation showed a statistically significant increased odds ratio adjusted for smoking among farmers; forestry workers, fishermen, and livestock workers; miners and quarrymen; chemical processors; cabinet makers and related wood workers; metal producers and processors; bricklayers and carpenters; road construction workers, pipelayers and well diggers; plasterers, insulators, and upholsterers; painters and lacquerers; stationary engine and heavy equipment operators; transport workers and freight handlers; and service workers. With regard to specific occupational exposures, elevated odds ratios (OR) (95% confidence intervals (CI)) for lung cancer risk adjusted for smoking and asbestos exposure were observed for man-made mineral fibers (OR = 1.48, 95% CI 1.17, 1.88); crystalline silica (OR = 1.41, 95% CI 1.22, 1.62); diesel engine exhaust (OR = 1.43, 95% CI 1.23, 1.67); and polycyclic aromatic hydrocarbons (OR = 1.53, 95% CI 1.14, 2.04). The risk of asbestos exposure, adjusted for smoking was also increased (OR = 1.41, 95% CI 1.24, 1.60).

Background: Although in several epidemiological studies exposure to diesel motor emissions (DME) shows an elevated lung cancer risk, it is still controversial whether DME is a human carcinogen., Methods: In a pooled analysis of two case-control studies on lung cancer in Germany a total of 3498 male cases with histologically or cytologically ascertained lung cancer and 3541 male population controls were included. Information about lifelong occupational and smoking history was obtained by questionnaire. Drivers of lorries, buses, taxies, diesel locomotives and forklift trucks, bulldozers, graders, excavators, and tractors, were considered as exposed to DME and their cumulative exposure was estimated. All odds ratios were adjusted for smoking and asbestos exposure., Results: The evaluation of lung cancer risk for all jobs with DME-exposure combined showed an odds ratio of OR=1.43 (95%-CI: 1.23-1.67). Most pronounced was the increase in lung cancer risk in heavy equipment operators (OR=2. 31 95%-CI: 1.44-3.70). The risk of tractor drivers increased with length of employment and reached statistical significance for exposures longer than 30 years (OR=6.81, 95%-CI: 1.17-39.51). The group of professional drivers (e.g., trucks, buses, and taxies), showed an increased risk only in West Germany (OR=1.44, 95%-CI: 1. 18-1.76), but not in East Germany (OR=0.83, 95%-CI: 0.60-1.14). DME-exposure in other traffic related jobs (e.g., diesel engine locomotive drivers, switchmen, forklift operators) was associated with an odds ratio of OR=1.53 (95%-CI: 1.04-2.24)., Conclusions: The study provides further evidence that occupational exposure to diesel motor emissions is associated with an increased lung cancer risk., (Copyright 1999 Wiley-Liss, Inc.)

Objectives: This study evaluated whether occupational exposure plays a role for lung cancer at a very young age., Methods: In a pooled analysis of 2 German case-referent studies including 3498 incident cases among men and 3541 male population referents, a group of men (187 cases and 202 referents) aged > or =45 years was compared with a group of 2186 cases and 2146 referents aged 55-69 years. Occupational exposure to known (A list) or suspected (B list) lung carcinogens was assessed using job and industry codes, and exposure to asbestos was assessed using job-specific supplementary questionnaires. A conditional logistic regression was used to calculate the odds ratios (OR) and to control for smoking., Results: Asbestos exposure showed an odds ratio (OR) of 2.39 [95% confidence interval (95% CI) 1.41-4.04] for the younger group and 1.46 (95% CI 1.24-1.72) for the older group. Having ever worked in a job belonging to the A list as compared with never working in an A- or B-list job was associated with a significantly increased risk for the younger (OR 2.06, 95% CI 1.03-4.12) and older (OR 1.35, 95% CI 1.10-1.65) groups, adjusted for asbestos. Lung cancer risk for those working in A-list jobs at a very young age (under 16 years) was increased in the younger group (OR 6.14, 95% CI 1.41-28.01) in contrast to the older group (OR 1.19, 95% CI 0.91-1.63)., Conclusion: Occupational risk factors play an important role for lung cancer among young men. Early age at first exposure may favor an early age of the onset of lung cancer.

Background: To investigate the association between lung cancer and occupational factors in women., Methods: Six hundred eighty-six women with lung cancer and 712 controls matched for age and region were interviewed to gather occupational histories and information about other risk factors and confounders. Odds ratios (OR) and 95%-confidence intervals (CI) were calculated., Results: There were 11 cases and 2 controls who reported occupational asbestos exposure. Significantly elevated risks (P < 0.05, smoking-adjusted), were observed in the following industries: chemical, oil (OR 3.7), pottery, glass (OR 2.5), engine, vehicle building (OR 2.2), paper, wood, print (OR 1.9), cleaning service, hairdressing, housekeeping, waste disposal (OR 1.5); and occupations: assemblers, unskilled metal workers (OR 2.5), stock clerks, etc. (OR 1.6), restaurant owners and hoteliers (OR 2.7), as well as waitresses and travel attendants (OR 2.6)., Conclusions: The study provides evidence that both occupations previously observed as hazardous in males, and occupations of particular significance for women only, play a role in the risk of lung cancer in women.

In a case-control study, 839 male hospital-based cases of primary lung cancer and the same number of population-based controls--matched by sex, age, and region of residence--were personally interviewed for their job and smoking histories. The study allows to quantify occupational asbestos exposure that was thought to be a welding-associated risk: 6% of cases and 2% of controls were classified into the occupational category "welders or burners# (odds ratio [OR] = 2.65). This OR was reduced to 1.93 (95% confidence limit [CL]: 1.03-3.61) after adjustment for smoking and asbestos. In contrast, a history of welding in general for at least a half-year is 28% among cases and 23% among controls, yielding an OR of 1.25 (95% CL: 0.94-1.65) after adjustment for both confounders. The OR of welding for more than 6,000 hr is 1.45 (95% CL = 1.04-2.02), reduced to 1.10 after adjustment for smoking and asbestos. Oxyacetylene welding for more than 6,000 hr lifelong is associated with an OR of 1.86 (95% CL = 1.01-3.43) reduced to 1.46 (n.s.) after adjustment for smoking and asbestos. The risk of oxyacetylene welding seems to be highest for oat cell carcinoma with an adjusted OR for ever-exposure of 1.46 (95% CL = 0.69-3.10). Therefore, the present study supports the hypothesis that some, but not all, of the excess risk of welders observed in the literature may be due to a history of cigarette smoking and occupational asbestos exposure. The elevated risk for the subgroup of employees in the aircraft industry reported for the midterm evaluation of the study still prevails, though no longer statistically significant. However, employees in this industry who ever welded show an OR of 2.29 (95% CL = 1.19-4.42) after adjustment for smoking and asbestos.

Psychosocial factors in general, and the social and psychological conditions of work and occupation in particular, have attracted little attention to the epidemiological investigation into the occupational-related causes of lung cancer. There is some evidence available concerning the impact of loss events--including job losses--on cancer development. During our research presented in this article, we examined job changes and job transitions in the occupational biography of men with regard to their circumstances in terms of (in-)voluntariness both as individual events and the job-changing histories of individuals. We expected the job-changing histories of lung cancer cases to be more involuntary than those of population controls, and vice versa. Our sample contains 391 male case-control pairs. Cases are defined as newly-diagnosed men of German nationality with a histologically- or cytologically-confirmed diagnosis of primary lung cancer. Population controls were drawn randomly from the municipality records of residents and individuals matched to cases 1:1 by age and region. Occupational histories were reconstructed, and information about other classical and suspected risk factors was collected during standardized interviews by trained interviewers. We categorized the reported reasons for job changes, and classified them with respect to voluntariness on a seven-stepped rating scale from -3 'very involuntary' to +3 'very voluntary', defining relations within the empirically established categories. The job-changing histories of individuals are described by using the average score of voluntariness. We measured the degree of voluntariness for the occupational history: (1) by the rounded average score; and (2) by the quintiles of the average score. On the basis of individuals matched odds ratios (OR) estimates are derived for the score of voluntariness unadjusted and adjusted for smoking, asbestos exposure and socio-economic group by conditional logistic regression. The investigation into job-changing histories using the average score of voluntariness lead to similar results for both measuring methods for the total study group. When the rounded score was used, job-changing histories which were assessed as 'very involuntary' and 'involuntary' (score -3 and -2) showed an elevated odds ratio of adjusted 1.41 (95%-CI: 0.57; 3.48), and when they were assessed as 'moderately involuntary' (score -1) the adjusted odds ratio was 1.59 (95%-CI: 1.02; 2.48), as compared with job-changing histories assessed as neutral (score 0). When the degree of voluntariness was measured by quintiles, the first quintile (score -3- < -0.6) showed an elevated risk of adjusted OR 1.36 (95%-CI: 0.79; 2.36) as compared to the third quintile (score -0.2- < -0.1).(ABSTRACT TRUNCATED AT 400 WORDS)

Retrospective assessment of asbestos exposure--II. At the job level: Complementarity of job-specific questionnaire and job exposure matrices. International Journal of Epidemiology 1993; 22 (Suppl. 2): S96-S105. The assessments of asbestos exposure by two a priori job exposure matrices (JEM) and by a job-specific questionnaire (SQ) are compared at job level. The data used for the comparison were generated by an ongoing case-control study on lung cancer in a region of northern Germany with a relatively high past prevalence of asbestos exposure. Among job periods assessed as unexposed by either JEM, 96% are recognized as such by the SQ. Discrepancies between the SQ and JEM were observed in jobs rated potentially exposed by the JEM. Despite varying estimates, the JEM and SQ were consistent as regards the relative classification of job periods by probability of exposure. The concordance of the methods, estimated by Kappa statistics, was stronger for the two JEM than for either of the JEM and the SQ. The identification of specific occupation/industry combinations in which discrepancies were most frequent and the comparison with expert ratings in some jobs yield insights into the sources of the disagreement between the methods. The misclassification of exposure by the JEM usually results in an overestimation of exposure. This is essentially related to loss of information due to the use of job codes as surrogates for job task descriptions and to the insufficiency of published data on asbestos exposure in different industries. As regards the SQ, two main sources of potential loss of sensitivity were identified: 1) possible omission of indirect sources of exposure by this method, 2) possible incompleteness of the SQ. The present comparison of methods of asbestos exposure assessment does not allow any one approach to be considered superior to another. Indeed, as proposed by Ahrens et al. in Part I of the study, both should be used to ensure optimal epidemiological performance.

Retrospective assessment of asbestos exposure--I. Case-control analysis in a study of lung cancer: efficiency of job-specific questionnaires and job exposure matrices. International Journal of Epidemiology 1993; 22 (Suppl. 2): S83-S95. In a lung cancer study in Northern Germany the asbestos exposure assessment obtained from detailed supplementary questionnaires (SQ) was compared to the assessment obtained by the application of two job exposure matrices (JEM) to the job history. The study includes 391 incident male cases and the same number of controls from the general population, matched by sex, age, and region. Almost 16% of the subjects are considered as never having been exposed to asbestos and 24% are classified as certainly exposed according to both of the JEM, the corresponding percentages of the SQ-method being 68% and 32%. Sixty percent are considered by the JEM as having an intermediate probability of exposure. In general, the agreement between the different methods is better when the exposure definition is restricted to definite exposures, the corresponding Kappa statistic being 0.67 for the comparison between both JEM and 0.44/0.39 between the JEM and the SQ. The positive agreement between SQ and JEM (reference) increases from 12% and 17% for subjects with low probability of exposure to 61% and 69% for those with definite exposures. A ranking according to cumulative exposure shows some dose-response relationship for each of the three methods with a smoking-adjusted OR in the highest category of 1.85 (95% CI: 1.01-3.38) for the SQ method and 2.47 (95% CI: 1.40-4.37) and 2.94 (95% CI: 1.73-4.99) for the two JEM. The results are discussed with reference to the conceptual differences between the methods and their potential scope in future studies.