Prostate Cancer Prevention and the Selenium and Vitamin E Cancer Prevention Trial (SELECT): A Selenium Perspective

Abstract

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomized 35,533 healthy men, ≥55 years (≥50 years if African American), with normal digital rectal exams and prostate-specific antigens <4 ng/mL, to (i) 200 μg/day l-selenomethionine, (ii) 400 IU/day all-rac-alpha-tocopheryl acetate (vitamin E), (iii) both supplements, or (iv) placebo for a median of 5.5 years (range 4.2–7.3 years). The hypotheses underlying SELECT, that selenium and vitamin E individually and together decrease prostate cancer incidence, derived from epidemiologic and laboratory evidence and significant secondary endpoints in the Nutritional Prevention of Cancer (NPC) (selenium) and Alpha-Tocopherol Beta-Carotene (vitamin E) trials. Results from SELECT showed that prostate cancer incidence did not differ among the four arms: hazard ratios (HRs) (99% CIs) for prostate cancer: 1.13 (99% CI, 0.95–1.35; p = 0.06; n = 473) for vitamin E, 1.04 (99% CI, 0.87–1.24; p = 0.62; n = 432) for selenium, and 1.05 (99% CI, 0.88–1.25; p = 0.52; n = 437) for selenium + vitamin E vs. 1.00 (n = 416) for placebo. Statistically nonsignificant increased risks of prostate cancer with vitamin E alone (RR 1.13; p = 0.06) and newly diagnosed type 2 diabetes mellitus with selenium alone (RR 1.07; p = 0.16) were observed. SELECT data show that neither selenium nor vitamin E, alone or together, in the doses and formulations used, prevented prostate cancer in this heterogeneous population of healthy men. Although there are many potential explanations for the null findings in SELECT, the most likely reasons appear to be a mismatch between the target population and the intervention agents selected, or that effects were limited to as-yet-undetermined subgroups of susceptible men.