Effects of α-tocopherol and β-carotene supplementation on cancer incidence and mortality: 18-Year postintervention follow-up of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50-69 years, daily alpha-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas beta-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of alpha-tocopherol and beta-carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post-trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96-1.11) among beta-carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89-1.05) among alpha-tocopherol recipients compared with nonrecipients with the preventive effect of alpha-tocopherol continuing similar to 8 years postintervention. Body mass index significantly modified the effect of alpha-tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88-1.14) in normal-weight men, 0.87 (95% CI, 0.77-0.98) in overweight men, and 1.25 (95% CI, 1.01-1.55) in obese men. The post-trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98-1.05) for alpha-tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99-1.05) for beta-carotene recipients compared with nonrecipients. alpha-Tocopherol decreased post-trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70-0.99), whereas beta-carotene increased it (RR, 1.20; 95% CI, 1.01-1.42). In conclusion, supplementation with alpha-tocopherol and beta-carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate-dose alpha-tocopherol on prostate cancer continued several years post-trial and resulted in lower prostate cancer mortality.