title: Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer.
abstract: DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C --> T and 1298A --> C), methionine synthase (MS 2756A --> G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36-78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r=-0.573, P<0.001 and r=-0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=-0.311, P=0.01 and r=-0.356, P=0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively).
authors.affiliation: Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. maria.pufulete@kcl.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Pufulete
authors.forename: R
authors.initials: R
authors.lastname: Al-Ghnaniem
authors.forename: J A
authors.initials: JA
authors.lastname: Rennie
authors.forename: P
authors.initials: P
authors.lastname: Appleby
authors.forename: N
authors.initials: N
authors.lastname: Harris
authors.forename: S
authors.initials: S
authors.lastname: Gout
authors.forename: P W
authors.initials: PW
authors.lastname: Emery
authors.forename: T A
authors.initials: TA
authors.lastname: Sanders
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000428:Alcohol Drinking; D003106:Colon / Q000166:cytology* / Q000201:enzymology; D003113:Colonoscopy; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000201:enzymology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
chemical_list: D006710:Homocysteine; D004247:DNA; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase
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