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Departments of Medicine and Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; Division of Gastroenterology, St. Michael’s Hospital, Toronto, Ontario, Canada
3To whom correspondence should be addressed. E-mail: youngin.kim{at}utoronto.ca.
ABSTRACT
The inheritance of information based on gene expression levels is known as epigenetics, as opposed to genetics, which refers to information transmitted on the basis of gene sequence. In contrast to genetic changes observed in cancer, epigenetic changes are gradual in onset and are progressive, their effects are dose-dependent and are potentially reversible. These observations present new opportunities in cancer-risk modification and prevention using dietary and lifestyle factors and potential chemopreventive drugs. In this regard, folate, a water-soluble B vitamin, has been a focus of intense interest because of an inverse association between folate status and the risk of several malignancies (in particular, colorectal cancer) and of its potential ability to modulate DNA methylation. DNA methylation is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, in chromosomal modifications, and in the development of mutations. Aberrant patterns and dysregulation of DNA methylation are mechanistically related to colorectal carcinogenesis. Folate plays an essential role in one-carbon transfer involving remethylation of homocysteine to methionine, thereby ensuring the provision of S-adenosylmethionine, the primary methyl group donor for most biological methylation reactions. The portfolio of evidence from animal, human, and in vitro studies suggests that the effects of folate deficiency and supplementation on DNA methylation are gene and site specific, and appear to depend on cell type, target organ, stage of transformation, and the degree and duration of folate depletion.
KEY WORDS: • folate • colorectal cancer • epigenetics • DNA methylation
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