Folate and Vitamin B6 Intake and Risk of Colon Cancer in Relation to p53 Expression

Abstract

Considerable evidence suggests that a low-folate diet increases the risk of colorectal cancer, although the results of a recent randomized trial indicate that folate supplementation may not reduce the risk of adenoma recurrence. In laboratory models, folate deficiency appears to induce p53 mutation. We immunohistochemically assayed p53 expression in paraffin-fixed colon cancer specimens in a large prospective cohort of women with 22 years of follow-up to examine the relationship of folate intake and intake of other one-carbon nutrients to risks by tumor p53 expression. A total of 399 incident colon cancers accessible for p53 expression were available. The effect of folate differed significantly according to p53 expression (P(heterogeneity) = .01). Compared with women reporting folate intake <200 microg/day, the multivariate relative risks (RRs) for p53-overexpressing (mutated) cancers were 0.54 (95% confidence interval [CI], 0.36-0.81) for women who consumed 200-299 microg/day, 0.42 (95% CI, 0.24-0.76) for women who consumed 300-399 microg/day, and 0.54 (95% CI, 0.35-0.83) for women who consumed >or=400 microg/day. In contrast, total folate intake had no influence on wild-type tumors (RR, 1.05; 95% CI, 0.73-1.51; comparing >or=400 with <200 microg/day). Similarly, high vitamin B(6) intake conferred a protective effect on p53-overexpressing cancers (top versus bottom quintile: RR, 0.57; 95% CI, 0.35-0.94; P(heterogeneity) = .01) but had no effect on p53 wild-type tumors. We found that low folate and vitamin B(6) intake was associated with an increased risk of p53-overexpressing colon cancers but not wild-type tumors.