Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up

Context  In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, -tocopherol supplementation decreased prostate cancer incidence, whereas -carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants. Objective  To analyze postintervention effects of -tocopherol and -carotene on cancer incidence and total and cause-specific mortality. Design, Setting, and Participants  Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years May 1, 1993-April 30, 1999]) and total mortality (8 years May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received -tocopherol (50 mg), -carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review. Main Outcome Measures  Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality. Results  Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval CI], 0.94-1.20) among recipients of -carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving -tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for -tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for -carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for -carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases. Conclusions  The beneficial and adverse effects of supplemental -tocopherol and -carotene disappeared during postintervention follow-up. The preventive effects of -tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid -carotene supplementation.