PARP1,OGG1,XRCC1,XRCC2,XRCC3 Gene Polymorphisms And Breast Cancer Susceptibility

Breast cancer is a complex disease caused by multiple factors.In many theories of its pathogenesis,the variation of individual genetic genes is considered to play an important role in the susceptibility of breast cancer.The DNA damage repair system plays a key role in preventing the occurrence of cancer.In the DNA damage repair system,the individual differences in DNA damage repair ability are the key to determine the susceptibility of the tumor,and the DNA damage repair gene has a single nucleotide Morphology?single nucleotide polymorphisms,SNPs?is an important cause of individual differences in damage repair ability.Therefore,researches on DNA polymorphisms and breast cancer susceptibility for DNA damage repair genes,and the search for specific molecular markers are of great significance for the early diagnosis and treatment of breast cancer.In this study,DNA damage repair genes PAPR1,OGG1,XRCC1,XRCC2,XRCC3 were genotyped to analyze the correlation between their gene polymorphism sites and breast cancer clinical pathological parameters.Preliminary study on the correlation between the polymorphic loci and haplotypes of PAPR1,OGG1,XRCC1,XRCC2,XRCC3 genes and breast cancer susceptibility in breast cancer cases,exploring the interaction between different polymorphic loci of genes and breast cancer.The correlation between cancer susceptibility provides a reference for early diagnosis,treatment and prognosis evaluation of breast cancer.This study used Meta to select five DNA damage repair genes related to breast cancer susceptibility:PARP1,OGG1,XRCC1,XRCC2 and XRCC3.The distribution frequency of each polymorphic site was determined by Haploview software,and the TagSNP was screened by Tagger function.The selection criteria of Tag-SNPs were:MAF>0.05,r²>0.8,and 24 single nucleotide polymorphism sites were obtained by screening a total of 2210 subjects were recruited in this study.Among them,563breast cancer samples,379 benign breast samples and1268 healthy population samples.2 ml venous blood collected from subjects in an empty stomach,SNPs genotyping using TaqMan^?OpenArray^TM genotyping techniques.Preliminary statistical analysis of data using SPSS23.Through the R to analyse Hardy-Weinberg and single nucleotide polymorphism and disease correlation analysis.Haploview4.2was used for linkage imbalance LD analysis and haplotype and disease correlation analysis.MDR3.0.2 was used for gene interaction and breast cancer susceptibility correlation analysis.PAPR1,OGG1,XRCC1,XRCC2,XRCC3 gene polymorphisms and breast cancer susceptibility analysis results show that:PAPR1 gene rs1805408polymorphism is associated with breast cancer risk,PARP1 gene polymorphism is associated with breast There is no correlation between cancer risk;polymorphisms of two sites of OGG1 gene are not correlated with breast cancer risk;polymorphisms of XRCC1 gene rs3213263 and rs3213356 are related to breast cancer risk,other polymorphisms of XRCC1 There is no correlation between sex and breast cancer case group;different genotypes of XRCC2 gene rs3218536,rs3218408,rs3218408 locus are associated with breast cancer occurrence,and there is no correlation between XRCC2 other site polymorphism and breast cancer risk;XRCC3 gene rs1799794,Different genotypes at rs861534 and rs861530 loci were associated with breast cancer risk.Compared with normal control group,single nucleotide polymorphisms at other XRCC3 sites had no significant correlation with breast cancer risk.PAPR1,OGG1,XRCC1,XRCC2,XRCC3 gene haplotype and breast cancer susceptibility analysis results show that:in the PAPR1 gene,carrying haplotype CC may reduce the risk of breast cancer,carrying haplotype TT and haplotype TC The risk of individual occurrence is significantly increased.In the OGG1 gene,haplotypes CC and CG have a strong protective effect on the occurrence of breast cancer,which can effectively reduce the incidence of breast cancer.Carrying haplotype GG has a significant correlation with breast cancer.Carrying haplotype GG Of individuals have a significantly increased risk of breast cancer.In the XRCC1 gene,haplotypes CAA,TGG,and CAG have a strong protective effect on breast cancer;individuals with haplotype CGG have significantly increased risk of breast cancer.XRCC2 and XRCC3 gene haplotypes had no significant correlation with breast cancer susceptibility.Analysis of PARP1,XRCC1,XRCC2 gene polymorphism and breast cancer clinicopathological parameters showed that:PAPR1 gene rs1805415 polymorphism was associated with TNBC and PR?P=0.021;P=0.014?;PAPR1 gene rs1805408locus Polymorphisms were associated with TNBC,ER,and Ki67?P=0.018;P=0.019;P=0.032?.The rs25489 locus of XRCC1 gene was related to TNBC and ER?P=0.033;P=0.025?.The polymorphism of rs6964582 in XRCC2 gene was associated with P53?P=0.023?.PAPR1,OGG1,XRCC1,XRCC2,XRCC3 gene polymorphism site interaction and breast cancer susceptibility analysis results show that:PARP1,OGG1 and XRCC1 gene interaction analysis of 10 SNP sites showed that rs3213356,rs1805408,rs3213263 model combination There was a significant association with breast cancer susceptibility?P<0.001?.Interaction studies between 11 SNP sites of XRCC2 and XRCC3 genes showed that there was a significant association between the combination of rs3218536,rs861531,and rs3218438 models and breast cancer susceptibility?P<0.001?.The relationship between the polymorphic sites and haplotypes of the PAPR1,OGG1,XRCC1,XRCC2,XRCC3 genes and breast cancer susceptibility found in this study with further validation may be used as a molecular marker for the screening of high-risk breast cancer populations.Meanwhile,it has certain significance for early diagnosis and individualized treatment of breast cancer.