A Randomized, Double-Blind, Placebo-Controlled Investigation of Selenium Supplementation in Women at Elevated Risk for Breast Cancer: Lessons for Re-Emergent Interest in Selenium and Cancer

Abstract

Damage to cellular macromolecules such as DNA and lipid, induced via reactive oxygen species, and indicators of cell proliferation potential such as insulin-like growth factor (IGF) metabolic status are intermediate biomarkers of breast cancer risk. Based on reports that selenium status can affect these markers, a randomized, placebo-controlled, double-blind experiment was conducted to investigate the potential of selenium supplementation to modulate breast cancer risk. Using a placebo tablet or a tablet containing 200 μg selenium provided as high-selenium yeast daily for one year, concentrations of the biomarkers in blood or urine were assessed at baseline and after 6 and 12 months of intervention. The selenium intervention used in this study is presumed to mediate its effect via the induction of glutathione peroxidase activity and the consequential impact of the active form of this protein on oxidative damage. We found no evidence to support this hypothesis or to indicate that systemic IGF metabolic status was affected. Critical knowledge gaps must be addressed for the resurgence of interest in selenium and cancer to garner clinical relevance. Those knowledge gaps include the identification of a specific, high-affinity selenium metabolite and the cellular target(s) to which it binds, and the demonstration that the cellular determinant that the selenium metabolite binds plays a critical role in the initiation, promotion, or progression of a specific type of cancer.