Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression

Gastroenterology. 2008 Sep;135(3):770-80. doi: 10.1053/j.gastro.2008.06.033. Epub 2008 Jun 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control*
  • Diet*
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid Deficiency / complications
  • Genes, p53
  • Humans
  • Immunohistochemistry
  • Methionine / administration & dosage
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Risk Factors
  • Tumor Suppressor Protein p53 / metabolism*
  • Vitamin B 6 / administration & dosage*
  • Vitamin B 6 Deficiency / complications
  • Vitamin B Complex / administration & dosage*


  • Tumor Suppressor Protein p53
  • Vitamin B Complex
  • Vitamin B 6
  • Folic Acid
  • Methionine