Eva S Schernhammer1, Shuji Ogino, Charles S Fuchs. 1. Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. eva.schernhammer@channing.harvard.edu
Abstract
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 (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. CONCLUSIONS: 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.
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 tumorp53 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 (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. CONCLUSIONS: 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.
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