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Folate, DNA methylation and colo-rectal cancer

Published online by Cambridge University Press:  05 March 2007

Maria Pufulete ,
Peter W. Emery  and
Thomas A. B. Sanders
Maria Pufulete*
Affiliation:
Nutrition Food and Health Research Centre, King's College London, 150 Stamford Street, London, SE1 9NN, UK
Peter W. Emery
Affiliation:
Nutrition Food and Health Research Centre, King's College London, 150 Stamford Street, London, SE1 9NN, UK
Thomas A. B. Sanders
Affiliation:
Nutrition Food and Health Research Centre, King's College London, 150 Stamford Street, London, SE1 9NN, UK
*
*Corresponding author: Maria Pufulete, fax +44 207 848 4185, maria.pufulete@kcl.ac.uk
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Abstract

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Prospective cohort and case-control studies suggest an association between low folate intake and increased risk of colo-rectal adenoma and cancer. Some, but not all, animal studies indicate that folate supplementation protects against the development of colo-rectal neoplasms, although supraphysiological folate doses have been shown to enhance tumour growth. Folate is a methyl donor for nucleotide synthesis and biological methylation reactions, including DNA methylation. A low dietary folate intake may increase the risk of colo-rectal neoplasia by inducing genomic DNA hypomethylation, which can affect the expression of proto-oncogenes and tumour suppressor genes associated with the development of cancer. Common polymorphisms in genes involved in the methylation pathway, such as methylenetetrahydrofolate reductase and methionine synthase, have been shown to influence risk of colo-rectal neoplasia, with interactions dependent on folate status and/or alcohol intake, which is known to antagonise methyl group availability. There is some evidence to show that DNA from normal-appearing colo-rectal mucosa in individuals with colo-rectal cancer is hypomethylated. In a case-control study DNA methylation in normal-appearing colo-rectal mucosa has been shown to be lower in individuals with colo-rectal cancer (P=0.08) and colo-rectal adenoma (P=0.009) than in controls free of colo-rectal abnormalities. Human intervention trials to date suggest that supraphysiological doses of folate can reverse DNA hypomethylation in colo-rectal mucosa of individuals with colo-rectal neoplasia. In a double-blind randomised placebo-controlled study folate supplementation at physiological doses has been shown to increase DNA methylation in leucocytes (P=0.05) and colonic mucosa (P=0.09). Further studies are required to confirm these findings in larger populations and to define abnormal ranges of DNA methylation.

Keywords

FolateDNA methylationColo-rectal neoplasia
Type
Micronutrient Group Symposium on ‘Micronutrient supplementation: when and why?’
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 2 , May 2003 , pp. 437 - 445
Copyright
Copyright © The Nutrition Society 2003

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