Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site-specific cancers and any cancer. Single nucleotide polymorphisms strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2<0.3) were used as instrumental variables. Genetic associations of selenium-associated single nucleotide polymorphisms with cancer were obtained from the UK Biobank including a total of 59,647 cancer cases and 307,914 controls. Associations with p<0.1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180,000 individuals. The inverse-variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically-predicted TAB selenium levels were not associated with the risk of the 22 site-specific cancers or any cancer (all 22 site-specific cancers). Similarly, we observed no strong association for genetically-predicted blood selenium levels. However, genetically-predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio (OR) per one-unit increase in log-transformed levels, 0.83, 95% confidence interval (CI), 0.67-1.03) and multiple myeloma (OR, 1.40, 95% CI, 1.02-1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the meta-analysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI, 0.69-1.00). This study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well-powered studies.

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