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            <funder>Our study was supported by the German Social Accident Insurance, grant FP 271. Grant sponsors of the individual studies were the Canadian Institutes of Health Research and Guzzo-SRC Chair in Environment and Cancer, the Fondation de France, the German Federal Ministry of Education, Science, Research, and Technology (grants 01 HK 173/0 and 01 HK 546/8) and the Ministry of Labour and Social Affairs (grant IIIb7-27/13), EC's INCO-COPERNICUS Program, Polish State Committee for Science Research, Roy Castle Foundation, NIH/NCI/DCEG Intramural Research Program, Lombardy Region, INAIL and the European Union Nuclear Fission Safety Program, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, Europe Against Cancer Program, the Swedish Council for Work Life Research and the Swedish EPA, the University of Oviedo, the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101), the Ministry of Health of the Czech Republic—MH CZ—DRO (MMCI, 00209805), CIBERESP and FISS-PI060604.</funder>
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              <p>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.</p>
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