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

Background & Aims: 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. Methods: 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. Results: A total of 399 incident colon cancers accessible for p53 expression were available. The effect of folate differed significantly according to p53 expression (Pheterogeneity = .01). Compared with women reporting folate intake <200 μg/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 μg/day, 0.42 (95% CI, 0.24–0.76) for women who consumed 300–399 μg/day, and 0.54 (95% CI, 0.35–0.83) for women who consumed ≥400 μg/day. In contrast, total folate intake had no influence on wild-type tumors (RR, 1.05; 95% CI, 0.73–1.51; comparing ≥400 with <200 μg/day). Similarly, high vitamin B6 intake conferred a protective effect on p53-overexpressing cancers (top versus bottom quintile: RR, 0.57; 95% CI, 0.35–0.94; Pheterogeneity = .01) but had no effect on p53 wild-type tumors. Conclusions: We found that low folate and vitamin B6 intake was associated with an increased risk of p53-overexpressing colon cancers but not wild-type tumors.