Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis

J Inherit Metab Dis. 2011 Feb;34(1):101-9. doi: 10.1007/s10545-010-9128-0. Epub 2010 Jun 11.

Abstract

Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • DNA Damage / physiology*
  • DNA Methylation / physiology*
  • DNA Repair / physiology*
  • Epistasis, Genetic / drug effects
  • Folic Acid / blood
  • Folic Acid / metabolism
  • Folic Acid / pharmacology
  • Folic Acid / physiology*
  • Folic Acid Deficiency / complications
  • Folic Acid Deficiency / genetics
  • Humans
  • Models, Biological
  • Neoplasms / etiology*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology

Substances

  • Folic Acid