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

Lucock, Mark; Yates, Zoë; Martin, Charlotte; Choi, Jeong-Hwa; Beckett, Emma; Boyd, Lyndell; LeGras, Kathleen; Ng, Xiaowei; Skinner, Virginia; Wai, Ron; Kho, Jeremy; Roach, Paul; Veysey, Martin

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.

Citation

Lucock, M., Yates, Z., Martin, C., Choi, J.-H., Beckett, E., Boyd, L., LeGras, K., Ng, X., Skinner, V., Wai, R., Kho, J., Roach, P., & Veysey, M. (2015). Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence. Bba Clinical, 3, 107-112. https://doi.org/10.1016/j.bbacli.2014.11.005

• Journal Article Type: Article
• Acceptance Date: Nov 29, 2014
• Online Publication Date: Jan 5, 2015
• Publication Date: 2015-06
• Deposit Date: Apr 25, 2019
• Publicly Available Date: Apr 26, 2019
• Journal: BBA Clinical
• Print ISSN: 2214-6474
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Pages: 107-112
• DOI: https://doi.org/10.1016/j.bbacli.2014.11.005
• Keywords: Adenomatous polyp; Folate; Methionine; Vitamin B12; Vitamin B6; Homocysteine; Colorectal cancer; Diet
• Public URL: https://hull-repository.worktribe.com/output/1647389
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2214647414000312?via%3Dihub
• Contract Date: Apr 26, 2019