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.

Boston College Chestnut Hill Massachusetts USA

Cancer Epidemiology Unit Department of Medical Sciences University of Turin Turin Italy

Center for Research in Epidemiology and Population Health Team Exposome and Heredity U1018 Inserm University Paris Saclay Institut Gustave Roussy Villejuif France

Centre for Nutrition Prevention and Health Services National Institute for Public Health and the Environment Bilthoven The Netherlands

Dalla Lana School of Public Health University of Toronto Toronto Canada

Department of Cancer Epidemiology and Prevention Maria Sklodowska Curie National Research Institute of Oncology Warsaw Poland

Department of Cardiovascular Sciences and Public Health University of Padova Padova Italy

Department of Epidemiology and Prevention N N Blokhin National Medical Research Centre of Oncology Moscow Russia

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Environmental Research Group School of Public Health Imperial College London UK and National Research Council Palermo Italy

Epidemiology and Biostatistics Unit Centre Armand Frappier Santé Biotechnologie Institut national de la recherche scientifique Laval Quebec Canada

Epidemiology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Faculty of Health Sciences Palacky University Olomouc Czech Republic

Health Research Institute of Asturias University of Oviedo ISPA and CIBERESP Spain

Institute and Clinic for Occupational Social and Environmental Medicine University Hospital LMU Munich; Comprehensive Pneumology Center Munich Munich Germany

Institute for Medical Informatics Biometry and Epidemiology University of Duisburg Essen Essen Germany

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr University Bochum Germany

Institute for Risk Assessment Sciences Utrecht University Utrecht The Netherlands

Institute of Epidemiology Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Institute of Hygiene and Epidemiology 1st Faculty of Medicine Charles University Prague Czech Republic

International Agency for Research on Cancer Lyon France

ISGlobal Barcelona Spain

Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany

Masaryk Memorial Cancer Institute Brno Czech Republic

National Cancer Institute Bethesda Maryland USA

National Institute of Public Health Bucharest Romania

National Public Health Center Budapest Hungary

Occupational Cancer Research Centre Ontario Health Toronto Canada

Regional Authority of Public Health Banska Bystrica Slovakia

Roy Castle Lung Cancer Research Programme Department of Molecular and Clinical Cancer Medicine The University of Liverpool Liverpool UK

Stony Brook Cancer Center Stony Brook University Stony Brook New York USA

The Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

The Nofer Institute of Occupational Medicine Lodz Poland

Univ Rennes Inserm EHESP Irset UMR_S 1085 Pointe à Pitre France

University of Montreal Hospital Research Center Montreal Canada

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