Selenium and Vitamin E Cancer Prevention Trial

Abstract

Preclinical, epidemiological, and phase III data from randomized, placebo-controlled clinical trials suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. In vitro evidence suggests that selenium and vitamin E work synergistically to cause cell-cycle arrest, induce caspase-mediated apoptosis, and act as antiandrogens in arresting clonal expansion of nascent tumors. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), sponsored by the National Cancer Institute, is an intergroup Phase III, randomized, double-blind, placebo-controlled, population-based clinical trial designed to test the efficacy of selenium and vitamin E alone and in combination in the prevention of prostate cancer. The study has a 2 x 2 factorial design with a target accrual of 32,400. Eligibility criteria include an age of at least 50 years for African Americans and of at least 55 years for Caucasians; a DRE not suspicious for cancer; a serum PSA no greater than 4 ng/mL; and a normal blood pressure. Randomization will be equally distributed among the four study arms, with intervention consisting of a daily oral dose of study supplement (200 mug l-selenomethionine or 400 mg of racemic alpha-tocopheryl) or matched placebo. Study duration is planned for 12 years, with a 5-year uniform accrual period and a minimum of 7 and maximum of 12 years of intervention. The primary endpoint for SELECT is the clinical incidence of prostate cancer as determined by a recommended routine clinical diagnostic work-up, including yearly DRE and serum PSA level. SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001, with final results anticipated in 2013.

Intake of Selenium in the Prevention of Prostate Cancer: a Systematic Review and Meta-analysis*

“…However, we cannot exclude the possibility of confounding that may have influenced our results. The SELCT trial is an ongoing randomized trial designed to answer whether selenium and vitamin E prevent the risk of prostate cancer [30]. Until the publication of the results of this trial, we do not advise clinicians prescribe selenium for prostate cancer prevention.…”

Antioxidant Activity of Sulfur and Selenium: A Review of Reactive Oxygen Species Scavenging, Glutathione Peroxidase, and Metal-Binding Antioxidant Mechanisms

“…The results indicated that daily supplementation with selenium-enriched yeast (200 lg/day) caused a 63% reduction in prostate cancer, 58% reduction in colorectal cancer, and 46% reduction of lung cancer [214]. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) trial investigated the chemopreventive effects of selenium and vitamin E on prostate cancer in 32,400 men and found no effect [158,215]. The Third National Health and Nutrition Examination Survey conducted by Bleys et al measured the selenium serum concentration in 13,887 adults and determined that increasing selenium levels were associated with a decrease in deaths due to cancer [216].…”

The Anti-inflammatory Effects of Selenium Are Mediated through 15-Deoxy-Δ12,14-prostaglandin J2 in Macrophages

“…Cardiomyopathy and rhabdomylosis are characteristics of selenium deficiency (37). Recently, supplementation with selenium has been positively correlated with lowered incidences in prostate cancer and HIV replication, where macrophage activation is a crucial step in the inflammatory processes that form the underlying basis of disease progression (38). Here we show that selenium supplementation of macrophages downregulates the expression of COX-2, via the inhibition of the enzymatic activity of IKK␤ by covalent modification of an essential Cys residue within its activation loop by 15d-PGJ 2 .…”