Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY)
Ann Olsson, Liacine Bouaoun, Joachim Schüz, Roel Vermeulen, Thomas Behrens, Calvin Ge, Hans Kromhout, Jack Siemiatycki, Per Gustavsson, Paolo Boffetta, Benjamin Kendzia, Loredana Radoï, Christine Barul, Stefan Karrasch, Heinz‐Erich Wichmann, Dario Consonni, Maria Teresa Landi, Neil E. Caporaso, Franco Merletti, Enrica Migliore, Lorenzo Richiardi, Karl‐Heinz Jöckel, Wolfgang Ahrens, Hermann Pohlabeln, Guillermo Fernández‐Tardón, David Zaridze, John K. Field, Jolanta Lissowska, Beata Świątkowska, John R. McLaughlin, Paul A. Demers, Miriam Schejbalová, Lenka Foretová, Vladimír Janout, Tamás Pándics, Eleonóra Fabiánová, Dana Mateș, Francesco Forastiere, Kurt Straíf, Thomas Brüning, Jelle Vlaanderen, Susan Peters
Abstract
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: = 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.