Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan

Nutr Cancer. 2005;53(1):42-50. doi: 10.1207/s15327914nc5301_5.


We conducted a case-control study to investigate the association of nutrient intake involved in the one-carbon pathway of folate for DNA methylation and DNA synthesis and the related enzyme genetic polymorphisms with colorectal cancer. Cases were 107 patients newly diagnosed with colorectal cancer. Controls were 224 subjects matched with cases by sex, age, and residential area. Nutrient intake was assessed by a self-administered, semiquantitative food-frequency questionnaire. Four genetic polymorphisms-MTHFR C677T and A1298C, MTRR A66G, and ALDH2 Glu487Lys-were determined using blood samples. Odds ratios were calculated using conditional logistic regression analysis adjusted for smoking, alcohol consumption, body mass index, and dietary fiber intake. Although folate intake was inversely associated with colorectal cancer, this association was attenuated after further controlling for dietary fiber intake. Neither vitamin B6, vitamin B12, nor vitamin B2, nor any genetic polymorphism was significantly associated with colorectal cancer. MTRR polymorphism interacted with the association of folate (P for interaction = 0.04) or vitamin (P for interaction = 0.02) with colorectal cancer, although the other polymorphisms did not interact with any nutrient intake. In conclusion, the study did not support the existing hypothesis of gene-nutrient interaction in colorectal carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aldehyde Dehydrogenase / genetics
  • Carbon-Nitrogen Ligases / genetics
  • Case-Control Studies
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • DNA Methylation*
  • Diet
  • Dietary Fiber / administration & dosage
  • Female
  • Ferredoxin-NADP Reductase / genetics
  • Folic Acid / administration & dosage
  • Humans
  • Japan / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Riboflavin / administration & dosage
  • Risk Factors
  • Surveys and Questionnaires
  • Vitamin B 12 / administration & dosage
  • Vitamin B 6 / administration & dosage
  • Vitamin B Complex / administration & dosage*


  • Dietary Fiber
  • Vitamin B Complex
  • Vitamin B 6
  • Folic Acid
  • Ferredoxin-NADP Reductase
  • Aldehyde Dehydrogenase
  • Carbon-Nitrogen Ligases
  • 5,10-methenyltetrahydrofolate synthetase
  • Vitamin B 12
  • Riboflavin