Selenium exposure and risk of skin cancer: A systematic review and dose-response meta-analysis of epidemiologic evidence

Background: Controversies still exist about the effects of selenium exposure on skin cancer risk. Methods: We performed a systematic literature search of non-experimental and experimental studies investigating the relation between selenium and risk of melanoma and non-melanoma skin cancers (NMSC) in adults. Results: We identified 26 studies, 19 of which were suitable for quantitative meta-analysis. In non-experimental studies, serum/plasma selenium concentrations showed slightly lower risk of NMSC, while no change in risk was observed for toenail or dietary selenium. Dose-response meta-analysis showed a general decreasing NMSC risk with increasing selenium serum/plasma concentrations, while there was no change in risk at any level of toenail selenium concentration. In experimental studies, we observed a higher risk for squamous cell carcinoma (risk ratio 1.25, 95 % confidence interval 1.04-1.49), but not basal cell carcinoma or NMSC overall in selenium-supplemented participants. In dose-response analysis of non-experimental studies, we observed little association between selenium exposure and melanoma risk, with limited evidence of increased risk for low (<100 µg/L) serum selenium. Using toenail concentrations, we found an inverted U-shaped pattern, with a lower melanoma risk at both low and high selenium concentrations, likely due to differences in risk across cohort and case-control studies showing positive and null associations, respectively. An excess risk following environmental selenium exposure through drinking water was noted. In experimental studies, selenium supplementation was associated with higher but imprecise melanoma risk (risk ratio 1.24, 95 % confidence interval 0.57-2.68). Conclusion: Overall, selenium exposure does not appear to influence basal cell carcinoma risk, but is associated with increased risk of squamous cell carcinoma and potentially melanoma.