Combined occupational exposure to carcinogenic metals/metalloids and risk of lung cancer

Introduction: Exposure to arsenic, cadmium, chromium (VI) and nickel increases the risk of lung cancer; whereas humans are exposed to mixtures, epidemiology studies refer to individual metals/metalloids. Methods: We analysed the data of a case-control study of lung cancer conducted in seven European countries and comprising 2861 cases and 2936 controls, with detailed assessment of occupational exposure to arsenic, cadmium, chromium (VI) and nickel, to estimate the odds ratio (OR) of lung cancer for combined exposure to these metals/metalloids, after adjustment for potential confounders. Results: Odds ratios for combined exposure to arsenic and cadmium and to arsenic and chromium (VI) were higher than those for individual metals (in order of 1.2-1.4 for single metals and above 2.0 for combined exposure), although formal tests of interaction on additive and multiplicative scales were imprecise and compatible with no interaction. Estimates for combined exposure to chromium (VI) and nickel were lower than expected under additive or multiplicative models, but confidence intervals for the interaction metrics included the null. Results for co-exposure to three or four metals/metalloids were based on small numbers of exposed subjects. Discussion: Findings provide limited evidence of statistical interactions between occupational exposure to these metals in relation to lung cancer risk.