Premium
Associations Between Folate, DNA Methylation, Methylenetetrahydrofolate Reductase Polymorphisms, and Colorectal Cancer Risk: A Review
Author(s) -
Miszewski Susan Grace,
Nazmi Aydin,
Derelian Doris
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.915.5
Subject(s) - methylenetetrahydrofolate reductase , genotype , dna methylation , epigenetics , biology , colorectal cancer , methylation , genetics , cancer research , cancer , gene , medicine , gene expression
A review of twelve studies showed consistent links between folate and colorectal cancer (CRC). Low dietary folate may lead to reduced levels of 5,10‐methylenetetrahydrofolate and accumulation of deoxsyuridylate in DNA which decreases DNA integrity and chromosomal breaks and increases CRC risk. Low dietary folate also leads to decreased DNA methylation; hypomethylation is suggested to inactive the p53 tumor suppressor gene. Folate deficiency produces strand breaks in human DNA, specifically in exons 5–8 of the p53 gene. These possible epigenetic factors depend on methylenetetrahydrofolate reductase genotype. Individuals with the 1298CC genotype showed lower risk of rectal cancer compared to those with the 1298AA or 1298AC genotypes. Individuals with the 677TT genotype showed reduced risk of rectal cancer when compared to those with the 677CT and 677CC genotypes. Levels of DNA methylation were consistently determined by folate status for those with the 677TT genotype, suggesting a possible role for plasma folate as an effect modifier among these individuals. Dietary folate status impacts risk for CRC via DNA methylation and chromosomal integrity, only in individuals with the 677TT genotype. Source of Support: None