The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia

• Published in: The American journal of clinical nutrition Vol. 98; no. 6; pp. 1564 - 1574
• Main Authors: Hanks, Joanna, Ayed, Iyeman, Kukreja, Neil, Rogers, Chris, Harris, Jessica, Gheorghiu, Alina, Liu, Chee Ling, Emery, Peter, Pufulete, Maria
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.12.2013; American Society for Clinical Nutrition, Inc
• Subjects: Adult; Aged; Aged, 80 and over; alleles; Biological and medical sciences; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; blood serum; clinical nutrition; Colon; Colon - enzymology; Colon - metabolism; Colorectal cancer; colorectal neoplasms; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - etiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Cross-Sectional Studies; Diet; Diet - adverse effects; DNA; DNA Methylation; electrospray ionization mass spectrometry; erythrocytes; estrogen receptors; Feeding. Feeding behavior; folic acid; Folic Acid - administration & dosage; Folic Acid - blood; Folic Acid - metabolism; Folic Acid Deficiency - blood; Folic Acid Deficiency - etiology; Folic Acid Deficiency - metabolism; Folic Acid Deficiency - physiopathology; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene-Nutrient Interactions; Genetic Association Studies; Genomics; genotype; Genotype & phenotype; homocysteine; Humans; insulin-like growth factor II; Intestinal Mucosa - enzymology; Intestinal Mucosa - metabolism; liquid chromatography; Medical sciences; men; methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); myoblasts; Nutritional Status; Polymorphism, Single Nucleotide; Risk; sequence analysis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; United Kingdom; United Kingdom - epidemiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamins; women; Young Adult; United Kingdom; Human; Rectal disease; Nutrition; Digestive system; Gut; Colorectal cancer; Genotype; Malignant tumor; Folic acid; Folate; Micronutrient; Colonic disease; Association; Gene; DNA; Digestive diseases; Intestinal disease; Colon; Methylation; Cancer
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.113.061432

Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation. We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon. We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively. Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001). MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia.