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Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis.

James Yarmolinsky1,2, Carolina Bonilla1,2, Philip C Haycock1,2

  • 1MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

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Selenium supplementation did not reduce prostate cancer risk and may increase the risk of advanced prostate cancer and type 2 diabetes. Mendelian randomization analysis supports these findings, suggesting caution with selenium supplements.

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Area of Science:

  • Nutritional epidemiology
  • Genetic epidemiology
  • Cancer prevention research

Background:

  • The Selenium and Vitamin E Cancer Prevention Trial (SELECT) found selenium supplementation did not lower overall prostate cancer risk.
  • SELECT indicated potential increased risks of high-grade prostate cancer and type 2 diabetes with selenium supplementation.
  • Mendelian randomization (MR) analysis offers a method to strengthen causal inference in observational studies by using genetic variants.

Purpose of the Study:

  • To investigate the causal effect of circulating selenium on prostate cancer risk using Mendelian randomization.
  • To assess the association between genetically elevated selenium levels and the risk of advanced prostate cancer and type 2 diabetes.

Main Methods:

  • Constructed a genetic instrument using 11 single nucleotide polymorphisms (SNPs) robustly associated with circulating selenium.
  • Performed Mendelian randomization analysis in the PRACTICAL Consortium (72,729 men) to evaluate selenium's effect on prostate cancer.
  • Utilized a large type 2 diabetes genome-wide association study meta-analysis for diabetes risk assessment.

Main Results:

  • Genetically elevated circulating selenium was not associated with overall prostate cancer risk (OR = 1.01, 95% CI = 0.89 to 1.13).
  • A weak association was observed between higher selenium levels and advanced prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49).
  • Higher selenium levels showed a weak association with increased type 2 diabetes risk (OR = 1.18, 95% CI = 0.97 to 1.43).

Conclusions:

  • Mendelian randomization analyses do not support selenium supplementation for prostate cancer prevention.
  • Findings suggest potential adverse effects of selenium supplementation on advanced prostate cancer and type 2 diabetes risks.
  • Caution is advised regarding the use of selenium supplements for cancer prevention due to potential risks.