Associated Study On The SNPs Of DNMT3A/3B Wih Genetic Susceptibility To Colorectal Cancer

Background and Objective:Colorectal cancer(CRC) is one of the common malignant gastrointestinal tumors in the world.Its development is more genes involved in complex process in each steps and stages. Abnormal DNA methylation in the inactivation of tumor suppressor genes is a kind of important epigenetic mechanisms of human malignant tumors.DNA methylation is mediated by a family of DNA methyltransferases(DNMTs).DNMT3A and DNMT3B is responsible for de novo methylation an it plays a crucial role in tumorigenesis.SNPs is to be single nucleotide polymorphism variation of the DNA sequence,which has become the third generation of genetic markers.MassARRAY technique is a flexible,accurate and efficient genetic analysis technology,and a suitable way for genotyping research with high throughput.In this study,we sought to investigate the genotype and alleledistribution characters and linkage disequilibrium of DNMT3A and DNMT3B gene polymorphism,then analyze its haplotypes.In order to explore the association of DNMT3A/3B SNPs with genetic susceptibility to colorectal cancer in tianjin.Methods:The randomly compared research method was used to analyze the89cases with colorectal cancer who had been hospitalized from January2011to June2012,94normal individuals were selected as controls according to the inclusion criteria.1.Genetic polymorphisms of DNMT3A and DNMT3B were analyzed in colorectal cancer patients and controls.the relation between DNMT3A and DNMT3B SNPs and colorectal cancer using MassARRAY method.2. Linkage disequilibrium (linkage disequilibrium, LD) analysis:some non-random banded alleles in different certain gene loci always are inherited toget her.LD of SNPs were measured by linkage ratio r2.3. Haplotype analysis:investigate the association of the overall genetic ha plotype with disease through the Pearson chi-square inspects.Results:1. There were no significant differences of genotypes between cases and controls in DNMT3A and DNMT3B SNPs(P>0.05).2. The difference of DNMT3A allele frequencies was not significant in cases with controlls.In the regulate area of DNMT3B,the genotypes containing Gallele of rs6119954and T allele of rs2424908were revealed with significantly protective effects against CRC(0.725vs0.628, P=0.047and0.585vs0.463,P=0.020).3. The data showed no evidence of pairwise linkage disequilibrium betwee n the four SNPs of DNMT3A.Strong linkage disequilibrium was found among six SNPs of DNMT3B (r2>0.8)4. We found significant association of haplotype TGTAGG and CATAGG with colorectal cancer.There were distinct differences between the cases and the controls in the haplotypes frequencies (P=0.0266, P=0.0264)Conclusions:1.DNMT3A gene SNPs might not have association with risk of colorectal cancer in the sudy.2. Association was found between rs6119954and rs2424908of DNMT3B SNPs with colorectal cancer in Chinese Han population.3. The haplotypes TGTAGG and CATAGG of DNMT3B gene might can be a predictor in colorectal cancer.