title: 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.
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.
authors.affiliation: 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. xiayu.wu@csiro.au.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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. xiayu98wu@163.com.
authors.forename: Weijiang
authors.initials: W
authors.lastname: Xu
authors.affiliation: 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. sn-xwj@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: 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. kmzl@163.com.
authors.forename: Neng
authors.initials: N
authors.lastname: Cao
authors.affiliation: 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. wy2057729@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Ni
authors.affiliation: Third Affiliated Hospital of Kunming Medical College, Kunming 650101, Yunnan, China. zoutn@aliyun.com.
authors.forename: Tianning
authors.initials: T
authors.lastname: Zou
authors.affiliation: 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. gt_gg30@163.com.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Liang
authors.affiliation: 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. wangxu@fudan.edu.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Genome Health and Personalized Nutrition, CSIRO Food and Nutrition, P.O. Box 10041, Adelaide SA 5000, Australia. michael.fenech@csiro.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics* / Q000378:metabolism; D042822:Genomic Instability; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D025101:Vitamin B 6 / Q000378:metabolism*
chemical_list: D025101:Vitamin B 6; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human
keywords: FMOCM; GSACV; breast cancer; gene-nutrient interaction; genetic polymorphisms; vitamin B6