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Int. J. Mol. Sci. 2016, 17(7), 1003; doi:10.3390/ijms17071003

The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients

1
School of Life Sciences, The Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education, Yunnan Normal University, Kunming 650500, Yunnan, China
2
Third Affiliated Hospital of Kunming Medical College, Kunming 650101, Yunnan, China
3
Genome Health and Personalized Nutrition, CSIRO Food and Nutrition, P.O. Box 10041, Adelaide SA 5000, Australia
*
Authors to whom correspondence should be addressed.
Academic Editor: Li Yang
Received: 11 May 2016 / Revised: 31 May 2016 / Accepted: 17 June 2016 / Published: 24 June 2016
(This article belongs to the Special Issue Tumor Microenvironment and Metabolism)
View Full-Text   |   Download PDF [2767 KB, uploaded 24 June 2016]   |  

Abstract

Folate-mediated one-carbon metabolism (FMOCM) is linked to DNA synthesis, methylation, and cell proliferation. Vitamin B6 (B6) is a cofactor, and genetic polymorphisms of related key enzymes, such as serine hydroxymethyltransferase (SHMT), methionine synthase reductase (MTRR), and methionine synthase (MS), in FMOCM may govern the bioavailability of metabolites and play important roles in the maintenance of genomic stability and cell viability (GSACV). To evaluate the influences of B6, genetic polymorphisms of these enzymes, and gene–nutrient interactions on GSACV, we utilized the cytokinesis-block micronucleus assay (CBMN) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques in the lymphocytes from female breast cancer cases and controls. GSACV showed a significantly positive correlation with B6 concentration, and 48 nmol/L of B6 was the most suitable concentration for maintaining GSACV in vitro. The GSACV indexes showed significantly different sensitivity to B6 deficiency between cases and controls; the B6 effect on the GSACV variance contribution of each index was significantly higher than that of genetic polymorphisms and the sample state (tumor state). SHMT C1420T mutations may reduce breast cancer susceptibility, whereas MTRR A66G and MS A2756G mutations may increase breast cancer susceptibility. The role of SHMT, MS, and MTRR genotype polymorphisms in GSACV is reduced compared with that of B6. The results appear to suggest that the long-term lack of B6 under these conditions may increase genetic damage and cell injury and that individuals with various genotypes have different sensitivities to B6 deficiency. FMOCM metabolic enzyme gene polymorphism may be related to breast cancer susceptibility to a certain extent due to the effect of other factors such as stress, hormones, cancer therapies, psychological conditions, and diet. Adequate B6 intake may be good for maintaining genome health and preventing breast cancer. View Full-Text
Keywords: FMOCM; vitamin B6; genetic polymorphisms; gene-nutrient interaction; GSACV; breast cancer FMOCM; vitamin B6; genetic polymorphisms; gene-nutrient interaction; GSACV; breast cancer
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Wu, X.; Xu, W.; Zhou, T.; Cao, N.; Ni, J.; Zou, T.; Liang, Z.; Wang, X.; Fenech, M. The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients. Int. J. Mol. Sci. 2016, 17, 1003.

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