title: Folate, colorectal cancer and the involvement of DNA methylation.
abstract: Diet is a major factor in the aetiology of colorectal cancer (CRC). Epidemiological evidence suggests that folate confers a modest protection against CRC risk. However, the relationship is complex, and evidence from human intervention trials and animal studies suggests that a high-dose of folic acid supplementation may enhance the risk of colorectal carcinogenesis in certain circumstances. The molecular mechanisms underlying the apparent dual modulatory effect of folate on colorectal carcinogenesis are not fully understood. Folate is central to C1 metabolism and is needed for both DNA synthesis and DNA methylation, providing plausible biological mechanisms through which folate could modulate cancer risk. Aberrant DNA methylation is an early event in colorectal carcinogenesis and is typically associated with the transcriptional silencing of tumour suppressor genes. Folate is required for the production of S-adenosyl methionine, which serves as a methyl donor for DNA methylation events; thereby folate availability is proposed to modulate DNA methylation status. The evidence for an effect of folate on DNA methylation in the human colon is limited, but a modulation of DNA methylation in response to folate has been demonstrated. More research is required to clarify the optimum intake of folate for CRC prevention and to elucidate the effect of folate availability on DNA methylation and the associated impact on CRC biology.
authors.affiliation: Department of Oncology, Human Nutrition Unit, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield S10 2RX, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Williams
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D005492:Folic Acid / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D014803:Vitamin B Complex / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid; D008715:Methionine