DNA methyltransferase and alcohol dehydrogenase: gene-nutrient interactions in relation to risk of colorectal polyps.

Publication Type:

Journal Article


Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Volume 17, Issue 2, p.330-8 (2008)


2008, Adenomatous Polyps, Adult, Aged, Alcohol Dehydrogenase, Center-Authored Paper, Colonic Polyps, Colonoscopy, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, Female, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Logistic Models, Male, Middle Aged, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Public Health Sciences Division, Shared Resources, Specimen Processing Core Facility


Disturbances in DNA methylation are a characteristic of colorectal carcinogenesis. Folate-mediated one-carbon metabolism is essential for providing one-carbon groups for DNA methylation via DNA methyltransferases (DNMTs). Alcohol, a folate antagonist, could adversely affect one-carbon metabolism. In a case-control study of colorectal polyps, we evaluated three single nucleotide polymorphisms (-149C>T, -283T>C, -579G>T) in the promoter region of the DNMT3b gene, and a functional polymorphism in the coding region of the alcohol dehydrogenase ADH1C gene, ADH1C *2. Cases had a first diagnosis of colorectal adenomatous (n = 530) or hyperplastic (n = 202) polyps at the time of colonoscopy, whereas controls were polyp-free (n = 649). Multivariate logistic regression analysis was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI). There were no significant main associations between the DNMT3b or ADH1C polymorphisms and polyp risk. However, DNMT3b -149TT was associated with an increase in adenoma risk among individuals with low folate and methionine intake (OR, 2.00; 95% CI, 1.06-3.78, P interaction = 0.10). The ADH1C *2/*2 genotype was associated with a possibly elevated risk for adenomatous polyps among individuals who consumed >26 g of alcohol/d (OR, 1.95; 95% CI, 0.60-6.30), whereas individuals who were wild-type for ADH1C were not at increased risk of adenoma (P interaction = 0.01). These gene-diet interactions suggest that polymorphisms relevant to DNA methylation or alcohol metabolism may play a role in colorectal carcinogenesis in conjunction with a high-risk diet.