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Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer?

Abstract

Epidemiological, clinical, and animal studies collectively indicate that dietary folate intake and blood folate levels are inversely associated with colorectal cancer risk. Folate plays an essential role in one-carbon transfer involving remethylation of homocysteine to methionine, which is a precursor of S-adenosylmethionine, the primary methyl group donor for most biological methylations. DNA methylation is an important epigenetic determinant in gene expression, maintenance of DNA integrity and stability, chromosomal modifications, and development of mutations. Dysregulation and aberrant patterns of DNA methylation are generally considered to be mechanistically involved in colorectal carcinogenesis. Aberrant DNA methylation has been considered as a leading mechanism by which folate deficiency enhances colorectal carcinogenesis. However, currently available data pertaining to the effects of folate deficiency on DNA methylation are inconsistent and incomplete. The portfolio of evidence from animal, human, and in vitro studies suggests that the effects of folate deficiency on DNA methylation are highly complex; appear to depend on cell type, target organ, and stage of transformation; and are gene and site specific. In addition, the pattern of site- and gene-specific DNA methylation induced by folate deficiency may not be in concert with the direction of changes in genomic DNA methylation. Collectively, currently available evidence indicates that genomic DNA hypomethylation in the colorectum is not a probable mechanism by which folate deficiency enhances colorectal carcinogenesis. However, there is still a possibility that sequence-specific alterations of DNA methylation in critical cancer-related genes might be mechanistically involved in the folate deficiency-mediated colorectal carcinogenesis.

Authors+Show Affiliations

Departments of Medicine and Nutritional Sciences, University of Toronto, Medical Sciences Building Room 7258, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. youngin.kim@utoronto.ca

Pub Type(s)

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

Language

eng

PubMed ID

15066913

Citation

Kim, Young-In. "Folate and DNA Methylation: a Mechanistic Link Between Folate Deficiency and Colorectal Cancer?" Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 13, no. 4, 2004, pp. 511-9.
Kim YI. Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers Prev. 2004;13(4):511-9.
Kim, Y. I. (2004). Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 13(4), pp. 511-9.
Kim YI. Folate and DNA Methylation: a Mechanistic Link Between Folate Deficiency and Colorectal Cancer. Cancer Epidemiol Biomarkers Prev. 2004;13(4):511-9. PubMed PMID: 15066913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? A1 - Kim,Young-In, PY - 2004/4/7/pubmed PY - 2005/2/16/medline PY - 2004/4/7/entrez SP - 511 EP - 9 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 13 IS - 4 N2 - Epidemiological, clinical, and animal studies collectively indicate that dietary folate intake and blood folate levels are inversely associated with colorectal cancer risk. Folate plays an essential role in one-carbon transfer involving remethylation of homocysteine to methionine, which is a precursor of S-adenosylmethionine, the primary methyl group donor for most biological methylations. DNA methylation is an important epigenetic determinant in gene expression, maintenance of DNA integrity and stability, chromosomal modifications, and development of mutations. Dysregulation and aberrant patterns of DNA methylation are generally considered to be mechanistically involved in colorectal carcinogenesis. Aberrant DNA methylation has been considered as a leading mechanism by which folate deficiency enhances colorectal carcinogenesis. However, currently available data pertaining to the effects of folate deficiency on DNA methylation are inconsistent and incomplete. The portfolio of evidence from animal, human, and in vitro studies suggests that the effects of folate deficiency on DNA methylation are highly complex; appear to depend on cell type, target organ, and stage of transformation; and are gene and site specific. In addition, the pattern of site- and gene-specific DNA methylation induced by folate deficiency may not be in concert with the direction of changes in genomic DNA methylation. Collectively, currently available evidence indicates that genomic DNA hypomethylation in the colorectum is not a probable mechanism by which folate deficiency enhances colorectal carcinogenesis. However, there is still a possibility that sequence-specific alterations of DNA methylation in critical cancer-related genes might be mechanistically involved in the folate deficiency-mediated colorectal carcinogenesis. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/15066913/full_citation L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15066913 DB - PRIME DP - Unbound Medicine ER -