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 (1) , Liacine Bouaoun (1) , Joachim Schüz (1) , Roel Vermeulen (2) , Thomas Behrens (3) , Calvin Ge (2) , Hans Kromhout (2) , Jack Siemiatycki (4) , Per Gustavsson (5) , Paolo Boffetta (6, 7) , Benjamin Kendzia (3) , Loredana Radoi (8, 9) , Christine Barul (10, 11) , Stefan Karrasch (12, 13, 14) , Heinz-Erich Wichmann (14, 15) , Dario Consonni (16) , Maria Teresa Landi (17) , Neil Caporaso (17) , Franco Merletti (18) , Enrica Migliore (18) , Lorenzo Richiardi (18) , Karl-Heinz Jöckel (19) , Wolfgang Ahrens (20, 21) , Hermann Pohlabeln (20) , Guillermo Fernández-Tardón (22) , David Zaridze (23) , John Field (24) , Jolanta Lissowska (25) , Beata Świątkowska (26) , John Mclaughlin (27) , Paul Demers (28) , Miriam Schejbalova (29) , Lenka Foretova (30) , Vladimir Janout (31) , Tamás Pándics (32) , Eleonora Fabianova (33, 34) , Dana Mates (35) , Francesco Forastiere (36) , Kurt Straif (37, 38) , Thomas Brüning (3) , Jelle Vlaanderen (2) , Susan Peters (2)

1 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
2 Universiteit Utrecht / Utrecht University [Utrecht]
3 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
4 University of Quebec at Montreal, Montreal, Quebec, Canada
5 Karolinska Institutet [Stockholm]
6 SBU - Stony Brook University [SUNY]
7 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
8 CESP - Centre de recherche en épidémiologie et santé des populations
9 U1018 (Équipe 3) - Épidémiologie des radiations, épidémiologie clinique des cancers et survie
10 Irset - Institut de recherche en santé, environnement et travail
11 EHESP - École des Hautes Études en Santé Publique [EHESP]
12 University-Hospital Munich-Großhadern [München]
13 CPC -M - Comprehensive Pneumology Center Munich [Munich, Germany]
14 HMGU - Helmholtz Zentrum München = German Research Center for Environmental Health
15 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
16 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
17 NCI-NIH - National Cancer Institute [Bethesda]
18 DMS - Department of Medical Sciences [Turin, Italy]
19 AöR - University Hospital Essen
20 Leibniz Institute for Prevention Research and Epidemiology - BIPS
21 Universität Bremen [Deutschland] = University of Bremen [Germany] = Université de Brême [Allemagne]
22 Universidad de Oviedo = University of Oviedo
23 N.N. Blokhin National Medical Research Center of Oncology
24 University of Liverpool
25 Maria Sklodowska-Curie National Research Institute of Oncology [Krakow, Poland]
26 NIOM - Nofer Institute of Occupational Medicine
27 University of Toronto
28 Public Health Ontario - Santé publique Ontario
29 1. LF UK / 1st Faculty of Medicine - 1. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = First Faculty of Medicine, Charles University [Prague, Czech Republic]
30 MMCI - Masaryk Memorial Cancer Institute
31 Palacky University Olomouc
32 National Public Health Center, National Directorate of Environmental Health, 1097 Budapest
33 Department of Epidemiology, Regional Authority of Public Health in Banská Bystrica
34 Pedagogical Faculty, Catholic University Ružomberok
35 RHL - National Institute of Public Health, Radiation Hygiene Laboratory, Bucharest
36 ASL - Azienda Sanitaria Locale [ROMA]
37 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
38 BC - Boston College

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.proxy.insermbiblio.inist.fr/10.1289/EHP13380.

Domaines: Sciences du Vivant [q-bio]

Ann Olsson, Liacine Bouaoun, Joachim Schüz, Roel Vermeulen, Thomas Behrens, et al.. Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY). Environmental Health Perspectives, 2024, 132 (1), pp.17005. ⟨10.1289/EHP13380⟩. ⟨hal-04443647⟩