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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) (Ptrend = 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 (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m3 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.). [ABSTRACT FROM AUTHOR]

Objective: The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons (by its proxy benzo(a)pyrene (BaP)) and respirable crystalline silica). A quantitative job-exposure matrix (JEM) was developed based on statistical modeling of large quantities of personal measurements. Methods: Empirical linear models were developed using personal occupational exposure measurements (n = 102 306) from Europe and Canada, as well as auxiliary information like job (industry), year of sampling, region, an a priori exposure rating of each job (none, low, and high exposed), sampling and analytical methods, and sampling duration. The model outcomes were used to create a JEM with a quantitative estimate of the level of exposure by job, year, andregion. Results: Decreasing time trends were observed for all agents between the 1970s and 2009, ranging from -1.2% per year for personal BaP and nickel exposures to -10.7% for asbestos (in the time period before an asbestos ban was implemented). Regional differences in exposure concentrations (adjusted for measured jobs, years of measurement, and sampling method and duration) varied by agent, ranging from a factor 3.3 for chromium-VI up to a factor 10.5 for asbestos. Conclusion: We estimated time-, job-, and region-specific exposure levels for four (asbestos, chromium-VI, nickel, and RCS) out of five considered lung carcinogens. Through statistical modeling of large amounts of personal occupational exposure measurement data we were able to derive a quantitative JEM to be used in community-based studies. [ABSTRACT FROM AUTHOR]

Background: Worldwide, lung cancer is the second leading cause of cancer death in women. The present study explored associations between occupational exposures that are prevalent among women, and lung cancer., Methods: Data from 10 case-control studies of lung cancer from Europe, Canada, and New Zealand conducted between 1988 and 2008 were combined. Lifetime occupational history and information on nonoccupational factors including smoking were available for 3040 incident lung cancer cases and 4187 controls. We linked each reported job to the Canadian Job-Exposure Matrix (CANJEM), which provided estimates of probability, intensity, and frequency of exposure to each selected agent in each job. For this analysis, we selected 15 agents (cleaning agents, biocides, cotton dust, synthetic fibers, formaldehyde, cooking fumes, organic solvents, cellulose, polycyclic aromatic hydrocarbons from petroleum, ammonia, metallic dust, alkanes C18+, iron compounds, isopropanol, and calcium carbonate) that had lifetime exposure prevalence of at least 5% in the combined study population. For each agent, we estimated lung cancer risk in each study center for ever-exposure, by duration of exposure, and by cumulative exposure, using separate logistic regression models adjusted for smoking and other covariates. We then estimated the meta-odds ratios using random-effects meta-analysis., Results and Conclusions: None of the agents assessed showed consistent and compelling associations with lung cancer among women. The following agents showed elevated odds ratio in some analyses: metallic dust, iron compounds, isopropanol, and organic solvents. Future research into occupational lung cancer risk factors among women should prioritize these agents., (© 2024 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

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.

Rationale: Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously., Objectives: Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma., Methods: The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case-control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking., Measurements and Main Results: Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20-1.48 and OR, 1.50; 95% CI, 1.21-1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33-4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis "only." Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter., Conclusions: Findings from this large international case-control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer.

The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.

Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development., (Copyright © 2011 UICC.)

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.

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.