XRCC6Gene Polymorphisms Associated With Risk Of Colorectal Cancer

Objective: We try to discuss the single nucleotide polymorphism (SNP) ofXRCC6gene rs5751129and rs2267437two loci and colorectal cancer (CRC)correlation risk through the case-control study, providing a molecular basis forthe diagnosis and treatment of colorectal cancer with favorable.Methods: Between Feb.2012-Feb.2013in the fourth affiliated hospitalof hebei medical university,78cases of colorectal cancer patients,51cases ofcolon cancer patients and74healthy people were chosed in case-controlstudy. Objects meet the conditions for the experiment collected venous bloodof5ml, and record the age, gender, smoking, drinking, family history andother information. The proteinase K digestion-saturated nacl salting outmethod to extract the the DNA in white blood cells, the Polymerase ChainReaction-ligase detection Reaction (PCR-LDR) was used to detect XRCC6gene and rs5751129C rs2267437C/G/T two SNP loci alleles and genotype.Experiment data using SPSS Ver13.0software package (SPSS Company inNew York, Chicago, Illionis, USA) for statistical analysis. Age difference inrectal cancer, colon cancer group and health control group were conducted byt-test; And gender differences between the two groups and the distribution ofallele frequency and genotype frequency distribution using the chi-square test,respectively. Hardy-Weinberg equilibrium analysis was performed bycomparing the observed and expected genotype. By unconditional logisticregression method to calculate represents the ratio of relative risk degree than(odds thewire, OR) and95%confidence interval (the confidence interval, CI).XRCC6gene in EH software and2ld-1310rs2267437C crs5751129c/T/Gand T-991two SNPs with combined analysis, P <0.05as there are significantdifference of the standard.Results: 1The distribution of the genotype frequencies of-1310rs2267437C/G andT-991Crs5751129C/T two loci were consistent with Hardy-Weinbergequilibrium (P>0.05).2XRCC6gene rs5751129C/T polymorphism and colorectal cancer riskcorrelation analysisThe frequency of rs5751129C XRCC6gene loci C and T in the coloncancer group was96.1%and3.9%,92.9%and7.1%in rectal cancer groupand94.6%and5.4%in control group, Compared in two groups, There werenot statistically significant difference in colorectal cancer and the controlgroup(P value was0.553and0.812), In the colon cancer group, T/T and C/Tgenotype frequency were92.2%and7.8%, while89.2%and10.8%in normalcontrol group, no significant difference (P>0.05), T/T genotype and C/Tgenotype carriers have no correlation with the incidence of colon and rectalcancer (OR=0.876,95%CI=0.239-3.214; OR=1.111,95%CI=0.368-3.353). The G allele may be a genetic markers of susceptibility in northernChina in the pathogenesis of CRC.3. rs2267437C XRCC6gene C/G polymorphism and colorectal cancer riskcorrelation analysisThe frequency of XRCC6gene rs2267437C/G locus allele C and G was78.4%and21.6%in colon cancer group,76.9%and23.1%in rectal cancergroup, in the normal control group were87.2%and12.8%, show that incontrast to rectal cancer and in the control group, the difference wasstatistically significant (P=0.02); There was no statistically significantdifference in comparison with the control group of colorectal cancer (P=0.67).In colon cancer,the frequencies of C/C,and C/G two kinds of genotype were56.9%and43.1%, in rectal cancer were53.8%and46.2%, while in the controlgroup were74.3%and25.7%, colon cancer and rectal cancer group andcontrol group for comparison, the differences were statistically significant (P=0.041, OR=2.196,95%CI=1.026-4.700; P=0.009, OR=2.481,95%CI=1.250-4.926).4Combined analysis of XRCC6colon cancer group and the control group of genes rs2267437C/G and rs5751129C/T two SNPs locus by EH software and2LD software. Display (Table5) unbalanced phenomenon linked XRCC6gene rs2267437C/G and rs5751129C/T two loci (D’=0.994). Haplotypers5751129T-population with rs2267437C (OR=1.250,95%CI=1.052~2.075),rs5751129T-rs2267437G haplotype (OR=0.846,95%CI=0.506~0.914),showed that the two kinds of genotype and colorectal cancer risk associatedwith. The other two haplotypes of OR and95%CI were0.406(95%CI=0.009~18.820),0.716(95%CI=0.209~2.449), showed that the twohaplotypes may have nothing to do with the risk of colorectal cancer.The combined analysis of XRCC6gene in colorectal cancer group andthe control group rs2267437C/G and rs5751129C/T two loci SNPs, display(Table6) unbalanced phenomenon linked XRCC6gene rs2267437C/G andrs5751129C/T two loci (D’=0.993). Four kind of monomers OR and95%CIwere0.598(95%CI=0.653~1.605),1.331(95%CI=0.519~3.413),1.024(95%CI=0.653~1.605),0.913(95%CI=0.579~1.439), showed that the fourhaplotypes may not be associated with the risk of colorectal cancer.Conclusion:1XRCC6gene T-991C(rs5751129) SNP may be not correlate to the incidenceof CRC.2XRCC6gene-1310(rs2267437) may be correlate to the incidence of CRC.Carrying the C/G genotype may increase the risk of CRC. The G allele may bea genetic markers of susceptibility in Hebei and its surrounding areas in thepathogenesis of CRC.3XRCC6gene rs5751129and rs2267437exsit a linkage disequilibriumbetween SNPs loci (D=0.994). rs5751129T-rs2267437C haplotype increasecolon cancer risk, rs5751129T-rs2267437G haplotype can reduce colon cancerrisk, the other two haplotype may not be associated with the risk of coloncancer. Analysing two sites of SNPs of XRCC6gene rs2267437C/G andrs5751129C/T in rectal cancer group and the control group of (D’=0.993), thefour kinds of haplotypes may not be associated with the risk of colorectalcancer. The combined analysis of XRCC6gene in colorectal cancer group andthe control group rs2267437C/G and rs5751129C/T two loci SNPs, display(Table6) unbalanced phenomenon linked XRCC6gene rs2267437C/G andrs5751129C/T two loci (D’=0.993). Four kind of monomers OR and95%CIwere0.598(95%CI=0.653~1.605),1.331(95%CI=0.519~3.413),1.024(95%CI=0.653~1.605),0.913(95%CI=0.579~1.439), showed that the fourhaplotypes may not associated with the risk of colorectal cancer.