Colon cancer and genetic variation in folate metabolism: the clinical bottom line

J Little, L Sharp, S Duthie, S Narayanan

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

So far, evidence for the relation between folate intake and colorectal cancer has been insufficient to lead to specific public health interventions. In principle, data on the relation between genetic variation in folate metabolism and colorectal neoplasia could be used to corroborate the data on the relation between folate intake or status and the disease, strengthening the evidence base for primary prevention. Issues in considering the relation between a health outcome and genetic variation in metabolism of nutrients or other food components include knowledge of gene function, linkage disequilibrium, population stratification, study size and quality, and gene-environment interaction. Overall homozygosity for MTHFR variant genotypes is associated with a reduced risk of colorectal cancer, the opposite of what might have been expected a priori. This has led investigators to place greater emphasis on the functions of folate and methylenetetrahydrofolate reductase in DNA synthesis. Folate and related nutrients may be important after adenoma formation. A challenge for the future is to characterize the effects of multiple genes influencing folate metabolism. Limited data for colorectal cancer suggest that the effect of a low folate diet overrides the effect of genotype, but two studies of adenomas suggested the opposite. Another potential role of information on genetic variation in folate metabolism is in the management of colorectal cancer but most studies have been small, have included selected patient groups, and have made limited adjustment for potentially important factors.

Original languageEnglish
Pages (from-to)3758S-3766S
Number of pages9
JournalThe Journal of Nutrition
Volume133
Issue number11 Suppl 1
Publication statusPublished - 2003

Keywords

  • colorectal neoplasia
  • folate
  • methylenetetrahydrofolate reductase epidemiology prevention
  • treatment
  • methylenetetrahydrofolate reductase gene
  • single nucleotide polymorphisms
  • methionine synthase gene
  • neural-tube defects
  • colorectal-cancer
  • 5,10-methylenetetrahydrofolate reductase
  • folic-acid
  • population stratification
  • thymidylate synthase
  • cardiovascular-disease

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    Little, J., Sharp, L., Duthie, S., & Narayanan, S. (2003). Colon cancer and genetic variation in folate metabolism: the clinical bottom line. The Journal of Nutrition, 133(11 Suppl 1), 3758S-3766S.