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

摘要

In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50-69 years, daily α-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α-tocopherol and β-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 β-carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89-1.05) among α-tocopherol recipients compared with nonrecipients with the preventive effect of α-tocopherol continuing ～8 years postintervention. Body mass index significantly modified the effect of α-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 α-tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99-1.05) for β-carotene recipients compared with nonrecipients. α-Tocopherol decreased post-trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70-0.99), whereas β-carotene increased it (RR, 1.20; 95% CI, 1.01-1.42). In conclusion, supplementation with α-tocopherol and β-carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate-dose α-tocopherol on prostate cancer continued several years post-trial and resulted in lower prostate cancer mortality. What's new? The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, begun in the mid-1980s, found that daily α-tocopherol supplementation decreased the risk of prostate cancer, whereas β-carotene increased the risk of lung cancer in Finnish male smokers. In the present study, a post-trial follow-up, neither α-tocopherol nor β-carotene were found to have significant effects on cancer incidence. The reduced risk of prostate cancer lasted about 8 years post-trial and was accompanied by decreased 18-year post-trial mortality from prostate cancer. BMI may modify the effect of α-tocopherol on prostate cancer, such that risk is decreased in overweight men but increased in obese men.