Selenium and cancer risk: Wide-angled Mendelian randomization analysis.

Area of Science:

• Nutritional Epidemiology
• Genetic Epidemiology
• Oncology

Background:

• The relationship between selenium exposure and cancer risk remains uncertain, with conflicting evidence.
• Selenium is an essential trace element involved in various biological processes, including antioxidant defense and immune function.
• Understanding selenium's role in cancer prevention is crucial for public health recommendations.

Purpose of the Study:

• To investigate the association between genetically predicted selenium levels and the risk of 22 site-specific cancers and overall cancer incidence.
• To utilize Mendelian randomization to infer causality and mitigate confounding factors present in observational studies.

Main Methods:

• A Mendelian randomization study design was employed using single nucleotide polymorphisms (SNPs) as instrumental variables for toenail and blood (TAB) and blood selenium levels.
• Genetic associations with cancer outcomes were analyzed in the UK Biobank (59,647 cases, 307,914 controls) and replicated in the FinnGen consortium (>180,000 individuals).
• The inverse-variance weighted method was used for meta-analysis, accounting for linkage disequilibrium.

Main Results:

• Genetically predicted TAB selenium levels showed no significant association with the risk of any of the 22 site-specific cancers or overall cancer.
• Genetically predicted blood selenium levels demonstrated a suggestive inverse association with kidney cancer risk (OR: 0.83, 95% CI: 0.67-1.03) and a positive association with multiple myeloma (OR: 1.40, 95% CI: 1.02-1.93).
• Replication in FinnGen supported the kidney cancer association, and meta-analysis confirmed this inverse association (OR: 0.83, 95% CI: 0.69-1.00).

Conclusions:

• This study suggests that high selenium status may not confer a protective effect against the development of most cancers.
• The observed suggestive associations for kidney cancer and multiple myeloma require further validation in larger, well-powered studies.
• Mendelian randomization provides valuable insights into the potential causal relationships between selenium and cancer risk.