Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence

Abstract

Purpose: The aim of this study is to explore whether a methylation diet influences risk for adenomatous polyps (AP) either independently, or interactively with one-carbon metabolism-dependent gene variants, and whether such a diet modifies blood homocysteine, a biochemical phenotype closely related to the phenomenon of methylation. Methods: 249 subjects were examined using selective fluorescence, PCR and food frequency questionnaire to determine homocysteine, nine methylation-related gene polymorphisms, dietary methionine, 5-methyltetrahydrofolate, vitamins B6 and B12. Results: 1). Both dietary methionine and 5-methyltetrahydrofolate intake are significantly associated with plasma homocysteine. 2). Dietary methionine is related to AP risk in 2R3R-TS wildtype subjects, while dietary B12 is similarly related to this phenotype in individuals heterozygous for C1420T-SHMT, A2756G-MS and 844ins68-CBS, and in those recessive for 2R3R-TS. 3). Dietary methionine has a marginal influence on plasma homocysteine level in C1420T-SHMT heterozygotes, while B6 exhibits the same effect on homocysteine in C776G-TCN2 homozygote recessive subjects. Natural 5-methyltetrahydrofolate intake is interesting: Wildtype A1298C-MTHFR, heterozygote C677T-MTHFR, wildtype A2756G-MS and recessive A66G-MSR individuals all show a significant reciprocal association with homocysteine. 4). Stepwise regression of all genotypes to predict risk for AP indicated A2756G-MS and A66G-MSR to be most relevant (p= 0.0176 and 0.0408 respectively). Results were corrected for age and gender. Conclusion: A methylation diet influences methyl group synthesis in the regulation of blood homocysteine level, and is modulated by genetic interactions. Methylation-related nutrients also interact with key genes to modify risk of AP, a precursor of colorectal cancer. Independent of diet, two methylation-related genes (A2756G-MS and A66G-MSR) were directly associated with AP occurrence.