Chd5 Gene Methylation And Folate Metabolism Genes In The Mthfr, Ms Polymorphism And Breast Cancer Relationship

Background & Objective:DNA methylation is mechanism which can influnce gene expression and related with tumorigenesis. The changes of DNA methylation state is a key factor not only for carcinogenesis,but also for tumor suppressor gene silence.Folate metabolism provides active methyl for organism methylation. Methylene tetrahydrofolate reductase(MTHFR) and Methionine synthase (MS) plays a vital role in the process of folate metabolism. This study aimed to explore the genetic polymorphism of MTHFR and MS, CHD5 methylation and their association with the breast cancer morbidity.Methods Forthy-seven patients with primary breast cancer,52 health Persons and 15 breast hyperplasia cases were enrolled. The mRNA exPression of CHD5 was determined by reverse transcriPtion PCR(RT-PCR). Methylation-sPecific PCR(MSP) was used to detect the methylation status of CHD5. Polymorphisms of MTHFR,MS gene was analyzed by polymerase chain reasction-restriction fragment length polymorphism (PCR-RFLP).Results The mRNA expression of CHD5 in breast cancer tissues(0.27±0.19) and adjacent non-cancerous tissues(0.33±0.17), both were significantly lower than that in breast hyperplasia tissues (0.67±0.14) (P<0.05). The percents of CHD5 methylation in breast cancer tissues and the adjacent non-cancerous tissues was 48.9%(23/47) and 17% (8/47) respectively, which was significantly different(P<0.05). The polymorphism distribution of MTHFR gene between C-allele and T-allele in cases and controls was statistical significance(P<0.05). Breast cancer risk associated with the MTHFR 677TT genotype was higher than MTHFR 677CC genotype(OR=5.44; 95%CI,1.91-15.48) There was statistical significance in the polymorphism distribution of MS gene between A-allele and G-allele(P<0.05). Breast cancer risk associated with the MS 2756AG genotype was higher than MS 2756AA genotype(OR=2.73; 95% CI,1.42-5.24). There was no significant relationship between the polymorphisms of MTHFR and the methylation of CHD5. Methylation of CHD5 was correlated with polymorphisms of MS2756 in breast cancer tissues(x2=4.85, P<0.05).Conclusion Methylation of CHD5 could contribute to the risk of breast cancer. MS gene polymorphism might regulate the expression of tumor-related genes by affecting the methylation status.