| BackgroundColorectal cancer(CRC)is one of the most common types of cancer in the world,the morbidity and mortality in China are increasing rapidly,the etiology and pathogenesis have not yet been fully elucidated.Evidences have showed that in addition to the environmental factors such as smoking,alcohol consumption,high red meat,high fat and low fiber intake,the genetic factor is closely related to the occurrence of colorectal cancer.First-degree relatives of patients with colorectal cancer have the significantly increased risk of colorectal cancer.Human genetic variation is most often derived from the single nucleotide polymorphisms(SNPs),there is evidence that SNPs may promote the occurrence of colorectal cancer.XPD,XPC,XRCC4 are the housekeeper genes of DNA repair gene family and play an important role in the repair process of double-stranded DNA mutations.Researches have showed that the polymorphism sites of XPD?XPC and XRCC4 can influence the expression and function of the XPD,XPC and XRCC4 protein and have closely relationships with the susceptibility of certain diseases such as malignant tumor,cardiovascular disease,rheumatoid arthritis,diabetes and so on.ObjectivesTo explore the association between the polymorphisms of XPD rs13181(codon751A/C),rs238406(codon 156C/A),XPC rs2279017(i11C/A),XRCC4 rs3734091(codon247T/C)and the susceptibility to CRC.Methods338 patients with CRC and 315 healthy controls at the same time and region were collected in this study and genomic DNA was extracted from venous blood.The genotypes of XPD rs13181?rs238406,XPC rs2279017 and XRCC4 rs3734091 were genotyped by TaqMan SNP genotyping assays.The Hardy-Weinberg equilibrium was assessed by the chi-square goodness-of-fit test.The haplotypes and haplotype frequencies were constructed and estimated using PHASE 2.1 software.The adjusted odds ratios(ORs)with 95%confidence intervals(95%CIs)adjusted for age,gender,smoking and alcohol consumption were derived from unconditioned logistic regression models to analyze the association of CRC susceptibility with genotypes/alleles/haplotypes.ResultsPatients of GT genotype and G allele frequencies at XPD rs13181 increased significantly compared with controls(GT,adjusted OR=1.69,95%CI=1.159-2.47,P=0.007;G allele,adjusted OR=1.77,95%CI=1.19-2.64,P=0.005).Patients of GT genotype and T allele frequencies at XRCC4 rs3734091 increased significantly compared with controls(GT,adjusted OR = 9.02,95%CI=5.61-14.50,P<0.001;G allele,adjusted OR=4.06,95%CI=2.49-6.61,P<0.001).For XPD rs238406 and XPC rs2279017,there was no significant finding in genotypic or allelic distributions between the two groups(P>0.05).The haplotype analysis revealed that the haplotype GT of XPD rs238406 and rs13181 showed a significantly decreased risk of developing CRC(adjusted OR= 0.39,95%CI=0.18-0.85,P=0.018).The combined effects showed that the combination of the G allele for XPC rs2279017 and the T allele for XRCC4 rs3734091 revealed a significantly increased susceptibility of CRC(adjusted OR=28.43,95%CI=6.85-117.95,P<0.001);the combination of the G allele for XPD rs13181 and the T allele for XRCC4 3734091 indicated a significantly increased risk of CRC(adjusted OR= 10.24,95%CI=4.69-22.35,P<0.001).Conclusions1.There is genetic polymorphism among XPD rs13181,rs238406,XPC rs2279017 and XRCC4 rs3734091;2.Genetic polymorphisms of XPD rs13181 and XRCC4 rs3734091 might associate with the susceptibility to CRC,while XPD rs238406 and XPC rs2279017 have no effects with CRC risk;3.Haplotype GT of XPD rs238406 and rs13181 is a risk factor for CRC;4.The associations between the combined effects of XPD?XPC?XRCC4 and CRC risk were significant.5.The polymorphisms of XPD rs13181 and XRCC4 rs3734091 might be efficient genetic markers for screening high risk individuals and conducting targeted intervention of CRC. |
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