SERUM ALPHA-TOCOPHEROL CONCENTRATION IN RELATION TO SUBSEQUENT COLORECTAL-CANCER - POOLED DATA FROM 5 COHORTS

Background: Vitamin E is an antioxidant that inhibits mutagenesis and cell transformation. Previous findings in five prospective epidemiologic studies suggested that the level of serum alpha-tocopherol, the predominant form of vitamin E in the blood, was lower in subjects who subsequently developed colorectal cancer than in control subjects. However, the difference was neither obvious nor statistically significant in any one of these five studies. Purpose: To evaluate in greater detail the association between serum alpha-tocopherol concentration and risk of colorectal cancer, we pooled and analyzed the original data from the five studies. Our analyses were designed to (a) test the hypothesis with greater statistical power, (b) examine the association after adjustment for serum cholesterol levels, and (c) evaluate the association after uniform exclusion of cases diagnosed shortly after blood specimens were drawn. Methods: Data for individual subjects were analyzed. To make the design of the component investigations uniformly nested case-control studies with individual matching, we matched controls to cases in two of the cohorts. Subjects were categorized according to study-specific quartile of serum alpha-tocopherol level within the study. The pooled analysis included 289 cases of colorectal cancer and 1267 matched controls. Results: For cancers of the colon and rectum combined, the matched odds ratio (OR) for the highest quartile of serum alpha-tocopherol concentration compared with the lowest was 0.6 (95% confidence interval [CI] = 0.4-1.0). Adjustment for serum cholesterol level attenuated the OR to 0.7 (95% CI = 0.4-1.1). Conclusion: The results suggest that serum alpha-tocopherol concentration may be inversely related to risk of colorectal cancer. It is unclear whether an association exists, however, because the association between serum alpha-tocopherol level and decreased risk of colorectal cancer was modest, the CIs were wide, and, overall, the tests for trend in effect were not significant. Implications: Larger observational studies with concurrent dietary data are needed to determine whether vitamin E has a modest but potentially important protective effect against colorectal cancer.