Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer

• Published in: British journal of cancer Vol. 92; no. 5; pp. 838 - 842
• Main Authors: Pufulete, M, Al-Ghnaniem, R, Rennie, J A, Appleby, P, Harris, N, Gout, S, Emery, P W, Sanders, T A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.03.2005; Nature Publishing Group
• Subjects: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics; Alcohol Drinking; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical Study; Colon - cytology; Colon - enzymology; Colonoscopy; Colorectal cancer; Cystathionine beta-Synthase - genetics; DNA - genetics; DNA Methylation; Drug Resistance; Enzymes; Epidemiology; Erythrocytes - metabolism; Female; Folic Acid - blood; Gastroenterology. Liver. Pancreas. Abdomen; Genotype & phenotype; Homocysteine; Homocysteine - blood; Humans; Intestinal Mucosa - cytology; Intestinal Mucosa - enzymology; Leukocytes; Male; Medical research; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; Molecular Medicine; Mutation; Oncology; Plasma; Polymorphism, Single Nucleotide; Reference Values; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumorigenesis; Tumors; Vitamin B; United Kingdom > UK; homocysteine; folate; colorectal cancer; CBS; MS; DNA methylation; MTHFR; genotype; Human; Rectal disease; Digestive system; Mucosa; Colorectal cancer; Malignant tumor; Folate; Colonic disease; Colorectal adenoma; Cancerology; Digestive diseases; Intestinal disease; Chromosome DNA; Benign neoplasm; Methylation
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602439

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).