8287735 Independent exposure-response analysis of five lung carcinogens and lung cancer risk in a cohort of 2.2 million Ontario workers

<h3>Objectives</h3> Several occupational exposures cause lung cancer, but few studies have examined sex-specific differences. We aim to investigate the independent exposure response effects of exposure to five carcinogens— asbestos, chromium VI, nickel, polycyclic aromatic hydrocarbons (PAHs), and silica — on lung cancer risk. <h3>Methods</h3> A prospective open cohort of Ontario workers was followed for lung cancer diagnoses from 1983 to 2019 in the Ontario Cancer Registry. Exposures were assessed using the Canadian job-exposure matrix, including measures for exposure status (exposed/non-exposed), intensity of exposure (low, medium/high) and frequency of exposure (&lt;8h/week, 8-40h/week, 40+h/week) for each carcinogen. Cox proportional hazards models estimated independent associations of carcinogen exposure and lung cancer risk overall, by sex, and by subtype. Models were adjusted for age, sex, and birth-year. <h3>Results</h3> Overall, 36,125 lung cancer cases were identified among 2,223,408 workers. Exposed workers had significantly higher lung cancer risks for all carcinogens (HR_chomium VI=1.12, 95% CI:1.06–1.18; HR_nickel=1.05, 95% CI: 1.01–1.10; HR_PAHs=1.18, 95% CI: 1.16–1.21; HR_silica=1.10, 95% CI: 1.06–1.14) except asbestos (HR_asbestos=1.00, 95% CI: 0.97–1.03). Females had higher risks than males for all carcinogens, ranging from 3% (Silica: HR_females=1.12, 95% CI: 0.96–1.31; HR_males=1.09, 95% CI: 1.05–1.13) to 28% (Nickel: HR_females=1.31, 1.10–1.56; HR_males=1.03, 95% CI: 0.99–1.08). Positive exposure-response relationships for exposure frequency and intensity were observed for all carcinogens, with stronger associations among females. Results were similar for adenocarcinoma, squamous cell, and small cell lung cancer. <h3>Conclusion</h3> The independent findings are consistent with previous research and highlight potential sex differences in lung cancer risk due to occupational exposure to five carcinogens.