Prostate Cancer and Supplementation With -Tocopherol and -Carotene: Incidence and Mortality in a Controlled Trial

Background: Epidemiologic studies have suggested that vitamin E and b-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of a-tocopherol (a form of vitamin E) and b-carotene supplementation, separately or together, on prostate cancer in male smokers. Methods: A total of 29 133 male smokers aged 50–69 years from southwestern Finland were randomly assigned to receive a-tocopherol (50 mg), b-carotene (20 mg), both agents, or placebo daily for 5–8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. Results: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = −47% to −12%) in the incidence of prostate cancer was observed among the subjects receiving a-tocopherol (n = 14 564) compared with those not receiving it (n = 14 569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = −65% to −1%) among men receiving a-tocopherol. Among subjects receiving b-carotene (n = 14 560), prostate cancer incidence was 23% higher (95% CI = −4%–59%) and mortality was 15% higher (95% CI = −30%–89%) compared with those not receiving it (n = 14 573). Neither agent had any effect on the time interval between diagnosis and death. Conclusions: Long-term supplementation with a-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings. [J Natl Cancer Inst 1998;90:440–6]