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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer?

Young-In Kim
Young-In Kim
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DOI:  Published April 2004
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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.

Footnotes

  • Grant support: Canadian Institutes of Health Research.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted December 5, 2003.
    • Received October 10, 2003.
    • Revision received December 2, 2003.
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Cancer Epidemiology Biomarkers & Prevention: 13 (4)
April 2004
Volume 13, Issue 4
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Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer?
Young-In Kim
Cancer Epidemiol Biomarkers Prev April 1 2004 (13) (4) 511-519;

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Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer?
Young-In Kim
Cancer Epidemiol Biomarkers Prev April 1 2004 (13) (4) 511-519;
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    • Abstract
    • Folate and Colorectal Cancer Risk
    • Mechanistic Understanding of the Folate Deficiency-Mediated Colorectal Carcinogenesis
    • DNA Methylation and Cancer
    • DNA Methylation Assays
    • Folate and DNA Methylation
    • The Effect of Methyl Group Deficiency on DNA Methylation in Rodents
    • The Effect of Folate Status on DNA Methylation in Humans
    • The Effect of Isolated Folate Deficiency on Genomic DNA Methylation in Rodent Liver and Colon
    • The Effect of Folate Deficiency on DNA Methylation in in Vitro Systems
    • Can Isolated Folate Deficiency Cause DNA Methylation Changes?
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