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

Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Cancer Causes and Control (Impact Factor: 2.74). 04/2000; 11(3):197-205.
Source: PubMed


Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer.
We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled 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, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models.
Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (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.
Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide 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.

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    • "Results from case-control studies were inconsistent7–17 and recent cohort studies have reported no clear relation.18–20 In addition, randomized trials of β-carotene supplementation provided no evidence to support an effect of carotenoids on colorectal cancer prevention.21,22 The carotenoid database for U.S. foods was recently updated to include various foods23; however, few studies in North America have used this updated database to examine intakes of individual carotenoids putatively related to colorectal cancer.13,15 "
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    ABSTRACT: A protective effect of fruits and vegetables against colorectal cancer has been supported by many epidemiologic studies. This suggests that the carotenoids frequently found in these foods play a role in the prevention of this common cancer. To examine associations between the intake of individual and total carotenoids and the risk of colorectal cancer, we analyzed prospective data from the Multiethnic Cohort Study. This analysis includes 85 898 men and 105 106 women who completed a quantitative food frequency questionnaire in 1993-1996. The participants were African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites aged 45-75 years at cohort entry. After an average follow-up of 8.2 years, 1292 and 1086 incident cases of colorectal cancer were identified in men and women, respectively. Cox proportional hazard models were used to estimate relative risks of colorectal cancer. No significant associations were found between intake of individual and total carotenoids and colorectal cancer risk either in men or women, except for beta-cryptoxanthin, which showed a mild protective effect in men. When the associations were investigated separately for colon and rectal cancer, lycopene intake was related to an increased risk of rectal cancer in men. A decreased risk was seen for total beta-carotene in male current smokers, but the test for interaction with smoking status was not significant. No association was observed in each ethnic-sex group. Overall, our findings do not support a significant association between carotenoid intake and colorectal cancer, although some associations were seen in subgroup analyses.
    Journal of Epidemiology 02/2009; 19(2):63-71. DOI:10.2188/jea.JE20080078 · 3.02 Impact Factor
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    • "This has been confirmed by several prospective observational studies which have shown that the use of vitamin supplements is associated with a lower risk for CVD (Morris and Carson, 2003). However, results of randomized clinical trials do not support a protective role of antioxidants in CAD (Hennekens et al., 1996; Rapola et al., 1997; Duffield-Lillico et al., 2003) or cancer (ATBC, 1994; Omenn et al., 1996; Albanes et al., 2000; Malila et al., 2002). Thus, it is concluded that the antioxidant status is only a marker of a diet rich in fruit and vegetables "
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    ABSTRACT: Low antioxidant intake and status have been shown to be associated with an elevated risk for various diseases. Data on the status of antioxidant vitamins, selenium and coenzyme Q10 of younger female seniors are scarce. The aim of this study was to assess the status of these antioxidants, as well as influencing factors such as dietary intake, anthropometric data and educational level in female seniors (60-70 years) in Germany. Dietary intake of alpha-tocopherol, beta-carotene and ascorbic acid was determined by a 3-day diet record. Serum concentrations of alpha-tocopherol, beta-carotene, ascorbic acid, selenium and coenzyme Q10 were measured. Anthropometric measures, socioeconomic and educational status were assessed. In total, 178 elderly women without severe diseases in the region of Hannover, Germany, were included in the study. The mean (+/- s.d.) age and BMI of the women was 63.2 (2.73) years and 25.6 (3.77) kg/m2, respectively. The study participants were generally better educated than the overall German female population. Dietary intake of the ascorbic acid and alpha-tocopherol was below RDA in six and 75% of the women, respectively. In comparison to estimated desirable serum concentrations of alpha-tocopherol, ascorbic acid, beta-carotene and selenium, lower concentrations were found in 23, 1, 6, and 39% of the women, respectively. Ascorbic acid (r = 0.205, P = 0.009) and beta-carotene (r = 0.173, P = 0.025) intake were significantly associated with serum concentrations. Beta-carotene concentrations were influenced by the type of diet, BMI, and school education (R2 = 0.128, P < 0.001). Serum selenium was positively associated with alcohol intake (r = 0.229, P = 0.003). Neither employment nor vocational training was predictive for the serum concentrations of antioxidant vitamins, selenium or coenzyme Q10. Poor status of selenium and alpha-tocopherol is highly prevalent even among younger, well-educated female seniors, whereas ascorbic acid and beta-carotene status seems sufficient in most women.
    European Journal of Clinical Nutrition 02/2006; 60(1):85-91. DOI:10.1038/sj.ejcn.1602271 · 2.71 Impact Factor
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    • "Trials evaluating beta-carotene alone [10,15–17], betacarotene combined with alpha-tocopherol [16] [17], or a combination of vitamins C and E [11] [15] reported null results regarding recurrent adenomas. Finally, a placebo-controlled trial showed a nonsignificant reduction in incident CRC [17], but a perplexingly significant increase in incident adenomas with alpha-tocopherol supplementation [16]. Null results have also been demonstrated with several pharmacologic agents. "
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    ABSTRACT: Colorectal cancer is expected to affect more than 146,000 and kill more than 57,000 Americans in 2004. Increased understanding of carcinogenesis is transforming clinical approaches to all stages of this disease. During the last 5 years, four new drugs have been approved for colorectal cancer treatment, and substantial progress has been made in identifying and developing agents that prevent or delay carcinogenesis. These advances substantiate target-driven approaches to cancer prevention and treatment, and provide fruitful opportunities for future investigations.
    Medical Clinics of North America 02/2005; 89(1):85-110, viii. DOI:10.1016/j.mcna.2004.08.003 · 2.61 Impact Factor
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