Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study

Ann Epidemiol. 2001 Jan;11(1):65-72. doi: 10.1016/s1047-2797(00)00188-5.


Purpose: This manuscript utilized the NHANES I Epidemiologic Follow-up Study (NHEFS), a national probability sample of the U.S. non-institutionalized population, to examine whether the intake of folate at baseline is associated with colon cancer risk.

Methods: The NHEFS consists of 14,407 subjects with 20 years of follow-up. Sociodemographic status, dietary information, family history of colon cancer, alcohol and aspirin use, smoking status, and body mass index (BMI) are included in the Cox proportional hazard model to examine confounding effects.

Results: After adjusting for confounders, a marginally significant association was observed between folate intake and reduced colon cancer risk. Gender and alcohol consumption appears to have an interactive effect with this association. The stratified results suggest that dietary folate is significantly inversely associated with colon cancer in men (relative risk (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.88) who consumed more than 249 microg/day of folate and that there is a significant dose-response relationship (p = 0.03). The association did not reach statistical significance in women. Using a composite dietary profile, we found that there is a significantly increased risk for men who consumed low-folate, low-methionine, and high alcohol diets when compared to male non-drinkers who consumed high-folate and high methionine diets (RR = 2.67, 95% CI = 1.16, 6.16).

Conclusions: This study found significant association between folate intake and reduced colon cancer risk among men and non-drinkers, but not women or drinkers. The study supports a synergistic interaction between intakes of folate, methionine and alcohol and colon cancer risk.

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking
  • Colonic Neoplasms / epidemiology*
  • Diet
  • Female
  • Folic Acid / administration & dosage*
  • Health Surveys
  • Humans
  • Male
  • Methionine / administration & dosage
  • Middle Aged
  • Nutritional Status*
  • Risk Factors
  • Smoking
  • United States / epidemiology


  • Folic Acid
  • Methionine