Association Of Genetic Polymorphisms In XRCC6,XRCC5 With Risk Of Esophageal Squamous Cell Carcinoma In An Yang,China

BackgroundEsophageal squamous cell carcinoma(ESCC)is the seventh leading cause of cancer-related deaths in the world.Epidemiologically,it is characterized by a distinctly higher incidence in certain geographical locations,such as China,especially in An Yang.Recent papers report that the high incidence of ESCC may result primarily from genetic rather than environmental factors which strengthens the importance of continuing to search for the genomic markers for esophageal cancer which are still largely unknown.The DNA repair systems are the genome caretakers,playing a critical role in the initiation and progression of cancers.However,the association between the genomic variations of DNA repair genes and cancer susceptibility is not well understood.This review focuses on the polymorphic genotypes of the non-homologous end-joining(NHEJ)DNA repair system,highlighting the role of two genes of this pathway,XRCC5 and XRCC6,in the susceptibility to ECSS.ObjectiveTo investigate the associations between polymorphisms and haplotypes in XRCC6,XRCC5 genes and ESCC susceptibility in Anyang area.MethodsXRCC6 rs2267437,XRCC5 rs3835 rs 16855458 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)in 189 ESCC patients and 189 cancer-free controls.Hardy-Weinberg equilibrium was evaluated by Chi-square test.Odds ratios(ORs)and 95%confidence intervals(CIs)were calculated by conditional univariate multivariate logistic regression as a measure of association with ESCC,adjusted for age,smoking and drinking status.Haplotype frequencies were estimated by Phase2.1.ResultsA significant difference in the genotype distribution and allele frequency of rs2267437(XRCC6)was observed between the cases and controls.The CG carriers were at higher risk of ESCC(p=0.001,odds ratio(OR)=2.040,95%confidence interval(95%CI)=1.323-3.147).G allele carries were also associated with an increased ESCC risk(p=0.003,OR=1.868,95%CI=1.230-2.836).In the two polymorphisms of XRCC5,no significant difference was found between both groups in the distribution of either genotype or allelic frequency.But in the haplotypes established by the Single Nucleotide Polymorphisms(SNP)of XRCC5,the haplotype AT and CC could separately increased 4.28 and 2.31 folds of the risk ratio of ESCC(p=0.01,OR=4.28,95%CI=1.40-13.05;p=0.03,OR=2.31,95%CI=1.11-4.80,respectively).Besides gene-smoking or gene-drinking on the risk of ESCC was observed,but no significant gene-environment interaction was demonstratedConclusionIn conclusion,both the CG carriers/G allele carries of rs2267437(XRCC6)and the haplotype AT/CC established by the SNPs of XRCC5 are associated with the ESCC susceptibility.