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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

Authors

Mark Lucock

Zoë Yates

Charlotte Martin

Jeong-Hwa Choi

Emma Beckett

Lyndell Boyd

Kathleen LeGras

Xiaowei Ng

Virginia Skinner

Ron Wai

Jeremy Kho

Paul Roach

Martin Veysey



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.

Journal Article Type Article
Publication Date 2015-06
Journal BBA Clinical
Print ISSN 2214-6474
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 3
Pages 107-112
APA6 Citation Lucock, M., Yates, Z., Martin, C., Choi, J., Beckett, E., Boyd, L., …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
DOI https://doi.org/10.1016/j.bbacli.2014.11.005
Keywords Adenomatous polyp; Folate; Methionine; Vitamin B12; Vitamin B6; Homocysteine; Colorectal cancer; Diet
Publisher URL https://www.sciencedirect.com/science/article/pii/S2214647414000312?via%3Dihub

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Copyright Statement
© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).



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