XRCC2Gene Polymorphisms Associated With Risk Of Colorectal Cancer

Background and Objective: Colorectal cancer is one of the commonmalignant neoplasm in the world,the mortality rate is ranked third,secondlyonly to gastric carcinoma and lung cancer.Colorectal cancer genesis anddevelopment is a multifactorial precess.DNA double-strand breaks can causethe chromosome unstably,at the same time induce tumor.XRCC2gene canrespire the DNA DSB,maintained genomic stability by homologousrecombination.The single nucleotide polymorphism of XRCC2influence thegenesis、development and therapeutic response of tumor by changing geneticexpression.Studies confirm that XRCC2gene has association with a widevariety of tumor,such as breast cancer、ovarian cancer、lung cancer andesophagus cancer,but the collection research of colorectal cancer is sofew.This research will use a case-control study to explore the relationship ofXRCC2rs3218536and rs3218408polymorphism with the risk of colorectalcancer in HeBei province.Methods: Between Feb.2012and Feb.2014in the fourth hospital ofHEBEI medical university,68cases of colorectal cancer patients,143cases ofcolon cancer patients and132random healthy people were selected for doingcase-control study.5ml of venous blood was collected on the object of theexperimental conditions including age, gender, smoking, alcohol consumption,family history and other information.The proteinase K digestion-saturatedsodium chloride salting out method and Polymerase Chain Reaction-ligasedetection Reaction (PCR-LDR) were used to handle obtaining samples anddetect XRCC2gene rs3218536A/G and rs3218408G/T two SNP loci allelesand genotype.Experiment data use SPSS Ver19.0software package (SPSSCompany in New York, Chicago, Illionis, USA) for statistical analysis. Agedifference in rectal cancer、colon cancer group and health control group were conducted by t-test; gender differences between the case and control groupsand the distribution of allele frequency and genotype frequency distributionuse the chi-square test, respectively,there are significant difference of thestandard when P <0.05.Hardy-Weinberg equilibrium was performed bycomparing the observed and expected genotype. The application ofnon-conditional logistic regression method to calculate the relative risk, oddsratio (odds ratio, OR) and95%confidence interval (confidence interval,CI).Results:1Demographic characteristicThe comparison of gender、age、smoking history and drinking historyhave no statistical significance between the colorectal group and controlgroup.The difference of family history between the colorectal group and controlgroup prove that family history maybe increase risk for colorectal in HEBEIprovince.(P value were0.001and0.004respectively in colon and rectal cancergroup.)2H-W equilibrium analysis of XRCC2rs3218536locus and rs3218408locusThe distribution of the genotype frequencies of rs3218536A/G andrs3218408G/T two loci were consistent with Hardy-Weinberg equilibrium(P>0.05).3XRCC2gene rs3218536A/G polymorphism and colorectal cancer riskcorrelation analysisThe frequency of rs3218536A/G XRCC2gene loci A and G in the controlgroup is20.8%（55/264） and79.2%（209/264）;13.2%（18/136）、86.8%（118/136）and25.5%（73/286）、74.5%（213/286）in colon cancer and rectalcancer group respectively.In the comparison of two heavy, no statisticalsignificance was found between haplotype A and G in colorectal cancer andthe control group(P value was0.062and0.193).The frequency of XRCC2allele genotype GG、AG and AA are65.2%（86/132）、28%（37/132） and 6.8%（9/132）in the control group, while the frequency are77.9%（53/68）、17.6%（12/68）、4.4%（3/68） in colon cancer group and60.8%（87/143）、27.3%（39/143）、11.9%（17/143） in rectal cancer group, which were notsignificant difference (P>0.05).XRCC2rs3218536SNP have no correlationwith the incidence of colon and rectal cancer (P value are0.084、0.336and0.881、0.151respectively in colon and rectal cancer group).4rs3218408G/T XRCC2gene G/T polymorphism and colorectal cancerrisk correlation analysisThe frequency of rs3218408G/T XRCC2gene loci T and G in the controlgroup is88.6%（234/264）and11.4%（30/264）,78.4%（107/136）、21.6%（29/136） and86.7%（248/286）、13.3%（38/286）in colon cancer and rectalcancer group respectively. Compared between three groups respectively,Pvalue are0.008and0.494respectively in colon and rectal cancer group,whichshow that in contrast between control group and the colon cancer group, thedifference was statistically significant (P=0.008),The consequence show thatrs3218408G allele possibly increase the risk of colon cancer in HeBeiprovince. The frequency of XRCC2allele genotype GG、GT and TT are2.3%（3/132）、18.2%（24/132）and79.5%（105/132）in the control group, whileGG、GT and TT genotype frequency are2.9%（2/68）、36.8%（25/68）、60.3%（41/68） in colon cancer group and2.1%（3/143）、22.4%（32/143）、77.5%（106/143） in rectal cancer group.In pairwise comparison between case andcontrol group,the P value are0.003、0.561and0.391、0.937respectively incolon and rectal cancer group.Through the analysis of the results,carrying theG/T gene type of individual has a higher risk of colon cancer in HEBEIprovince.5Combined analysis of XRCC2gene rs3218536locus and rs3218408locusCombined analysis of XRCC2colorectal cancer group and the controlgroup of genes rs3218536A/G and rs3218408G/T two SNP locus haplotypelinkage by EH software and2LD software. It is found that the haplotypesgenetic linkage between rs3218536A/G and rs3218408G/T exist complete linkage disequilibrium（D’=1）in colorectal cancer group. Discovered throughcomparative analysis,the OR of haplotype genetic linkagers3218536G-rs3218408G is2.114(95%CI=1.052~2.075), showed that thegenotype is associated with the colon cancer risk. The other two haplotypes ofOR and95%CI were0.580（0.325~1.033）、0.899（0.580~1.393）respectively, showed that the two haplotypes may have nothing to do with therisk of colon cancer.(Table5)The OR and95%CI of the rs3218536A-rs3218408T、 rs3218536G-rs3218408G、 rs3218536G-rs3218408T are1.302（0.874~1.940）、1.195（0.717~1.992）and0.749（0.527~1.063）in rectal cancer group, showed thatthree haplotypes maybe have no correlation with the risk of rectalcancer.(Table6)Conclusion:1XRCC2gene rs3218536A/G SNP may be not correlated with theincidence of colorectal cancer risk.2XRCC2gene rs3218408G/T SNP may be correlate to the incidence ofcolorectal cancer. Carrying the G/T genotype may increase the risk of CRC.The G allele may be a susceptive genetic markers of colon cancer in thepathogenesis in HeBei province.3The haplotypes genetic linkage exist complete linkage disequilibrium（D’=1） between rs3218536A/G and rs3218408G/T in colorectal cancergroup.The haplotype genetic linkage rs3218536G-rs3218408G maybe increasethe risk of colon cancer.The other two haplotype genetic linkage find nosignificant relationship of colon cancer.The above three kinds of haplotypegenetic linkage maybe have no correlation with the risk of rectal cancer.