Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland)

Background: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated wi th reduced risk of colorectal cancer. Methods: We tested the effects of alpha-tocopherol and beta-carotene supple mentation on the incidence of colorectal cancer in the Alpha-Tocopherol, Be ta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-control led trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene ( 20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, a nd 99% were histologically confirmed. Intervention effects were evaluated u sing survival analysis and proportional hazards models. Results: Colorectal cancer incidence was somewhat lower in the alpha-tocoph erol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interv al (CI) 0.55-1.09; log-rank test p = 0.15). beta-Carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. Conclusion: Our study found no evidence of a beneficial or harmful effect f or beta-carotene in colorectal cancer in older male smokers, but does provi de suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.