| The serinehydroxymethyhransferase (SHMT) reversible generates serine and methyleneTHF for thymidylate and methionine biosynthesis in folate metabolic pathway. It is therefore involved in numerous methylation reactions, which are closely related with DNA synthesis, methylation and the homocysteine (Hey) metabolism. Cystathionine-β synthase (CBS), methionine synthase (MS), methionine synthase reductase (MTRR) catalyze the homocysteine to form cystathionine or methyltetrahdrofolate through folate-mediated one-carbon metabolism or the transsulfuration pathway. So abnormality in CBS, MS, MTRR’s activity is manifested an important risk factors of vein thrombosis and other cardiovascular diseases. Vitamine B6(B6) as an important cofactor for SHMT and CBS also has the potential effect in the folate metabolism pathway.This research aimed to discusse the effects of B6and SHMT C1420T, CBS C699T/C1080T, MS A2756G, MTRR A66G polymorphism on human genome stability, Hey metabolism as well as to explore the mechanism of these actions on the risk factors of breast cancer by the radioimmunoassay, cytokinesis blocked micronucleus assay (CBMN) and PCR-RFLP technique.Results showed that (1) The plasma Hey of SHMT1420TT was significantly lower than that of the wild type, while the plasma Hey level of MS2756GG, CBS699TT/1080TT significantly higher than that of the wild type in case and the control group. The plasma Hey levels of MTRR66GG only in case group was significantly higher than that of wild type. The plasma Hey levels of the same genotype in case group were significantly higher than those of control group except SHMT1420CC, MS2756AA, MTRR66GG;(2) SHMT C1420T (OR=0.527,95%CI=0.55-1.24), MS A2756G (OR=2.32,95%CI=0.29-0.82), MTRR A66G (OR=1.84,95%CI=0.25-1.66) polymorphism is significantly associated with breast cancer risk;(3)The genetic damage markers[the micronucleus of binucleate cells (MNBN), nucleoplasmic bridge (NPB), nuclear buds (NBUD) and the micronucleus of monucleate cells (MONO)] frequencies of6-24nmol/L B6were increased significantly than48～200nmol/L B6 in the case and normal group. The APO, NEC of6,12nmol/L B6were significantly higher than that in24-200nmol/L B6, but there were no significant difference among24-200nmol/L;(4) All genetic damage and cytotoxic indexes showed negative correlation with B6concentration;(5) All indexes in case group were higher than those of the control, however the DDA analysis revealed that MNBN, MONO, NPB frequencies is significant different sensitivity to B6deficiency between those2groups;(6) B6on the genetic and cell damage variance contribution of each index was significantly higher than that of genotype and sample (tumor state);(7) MNBN frequency of SHMT1420CC genotype in various concentrations of B6were significantly higher than that of TT group in case group and control group. NBUD, APO and NEC frequencies in the6,12nmol/L B6while the NPB frequency only in6nmol/L of SHMT1420CC genotype was significantly higher than those of TT in case group. The MNBN frequency of MS2756GG in6-48nmol/L B6were significantly higher than that of AA genotype in cases group. The MONO, NBUD, NPB and NEC frequencies in6and12nmol/L while the APO frequency in6nmol/L significantly higher than that of TT in case group. The MNBN, MONO and APO frequencies of MTRR66GG in6nmol/L B6were significantly higher than those of AA in case and control group, NBUD frequency in6nmol/L B6was significantly higher than that of TT in case group.The research conclude the human genome instability can be induced by vitamin B6deficiency,48nmol/L B6was the most suitable concentration to maintain genomic stability of lymphocytes in vitro. SHMT C1420T mutation may reduce breast cancer susceptibility; while MS A2756G and MTRR A66G mutation may increase breast cancer susceptibility, But the role of polymorphisms of SHMT, MS, MTRR and CBS genotype polymorphism in the genome stability is less than B6. SHMT C1420T, MS A2756G, MTRR A66G, CBS C1080T, CBS C699T locus mutation may be a factor in affectting plasma level of Hcy. Hcy level is positively associated with breast cancer risk. The results suggest that the long-term lack of B6in the circumstances may increase the body’s genetic damage and cell injury, and individual with various genotypes has different sensitivity to B6deficiency. The Hcy metabolic enzyme genes polymorphism may be associated with breast cancer. So adequate B6intake at the same time may be reduce the concentration of plasma Hcy, which is good for preventing genome health and related diseases. |
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