Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

Int J Cancer. 2005 May 1;114(5):824-30. doi: 10.1002/ijc.20775.


We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / genetics*
  • DNA Mutational Analysis
  • Diet*
  • Female
  • Folic Acid / metabolism*
  • Genes, ras*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasms / metabolism
  • Netherlands
  • Rectal Neoplasms / etiology
  • Rectal Neoplasms / genetics*
  • Risk
  • Sex Factors


  • Folic Acid