The Study On The Relationship Between XRCC2Gene SNPs And Colorectal Cancer

Objective:To investigate the interaction between XRCC2C41657T G4234C SNPs and genetic susceptibility of colorectal cancer, the correlation the between the former and clinicopathologic features and discuss the influence of C41657T polymorphism on expression of XRCC2in colorectal cancer. The distribution of XRCC2gene C41657T G4234C single nucleotide polymorphisms in genotype and allele frequency of colorectal cancer patient was tested.Methods:Case-control study was used, and peripheral venous blood of2ml were obtained from colorectal cancer patients (n=246), and controls who have no tumor (n=262). At the same time, personal data, medical history and clinicopathologic features were collected. DNA was extracted by Phenol-chloroform-isopentyl alcohol Method. Genotype of XRCC2C41657T G4234C SNPs and distribution of allele were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). After that, the interaction between C41657T genotypes with colorectal cancer patients and cancer clinicopathologic features was compared.83cases of colorectal cancer tissue and36cases of normal colorectal tissue were collected. The expression of XRCC2protein in cancer and normal tissue were tested by immuno-histochemical staining (IHC) and the expression difference of protein was analyzed by chi-square test. The relationship between genotypes of C41657T and G4234C and the risk of cancer was studied by logistic analysis of regression. Odds ratio and95%confidential interval were calculated. Linkage disequilibrium and haplotype analysis were carried out by SHEsis online software. All statistical analysis results were calculated by software SPSS11.5and P<0.05was regarded as significant.Results:(1) Colorectal cancer patients and controls had no statistical difference in sex, age, smoking history and capacity for alcohol. Gene distribution of XRCC2C41657T and G4234C sites matched with Hardy-Weinberg Equilibrium (P>0.05).(2) Genotype frequency of XRCC2C41657T gene CC,CT,TT sites in cases was63.4%,33.3%,3.3%, and74.0%,23.3%,2.7%in controls, respectively. There was distribution difference of genotype frequency between two groups, which was of statistical significance (P<0.05). Genotype frequency of C, T allele in cases was80.1%,19.9%and85.7%,14.3%in controls, respectively. There was distinct difference between them (P<0.05). Genotype frequency of XRCC2gene G4234C GG, GC, CC sites in cases were67.5%,30.1%,2.4%, and72.9%,24.8%,2.3%in controls, respectively. There was no difference of genotype frequency between two groups, which was not of statistical significance (P>0.05). Genotype frequency of G, C allele in cases was82.5%,17.5%and85.3%,14.7%in controls, respectively. There was not distinct difference between them (P>0.05).(3) XRCC2gene C41657T SNP had relevance to risk of colorectal cancer. Compared to CC, CT and TT increased the risk of colorectal cancer (OR=1.646,95%CI=1.127～2.404). Compared to C allele, T allele increased the risk of CRC (OR=1.489,95%CI=1.071～2.071), while T allele was a risk factor of CRC. XRCC2gene G4234C SNP had no relevance to the risk of colorectal cancer. Compared to GG genotype, GC and CC could not increase the risk of colorectal cancer (OR=1.296,95%CI=0.885～1.898).(4) Distribution of genotype frequency of XRCC2C41657T in CRC was not different in clinicopathologic features such as structure position, general type, tumor histological type, differentiated degree, infiltration depth and lymph gland transfer (P>0.05).(5) The relevance between XRCC2C41657T polymorphism and its protein expression showed that expression ratio of XRCC2protein was44.58%in colorectal cancer structure. Compared to25.00%in normal structure, the difference was obvious (P=0.044). The expression ratio of XRCC2protein in colorectal cancer was significant difference between CC genotype and CT and TT genotype (x2=4.615, P=0.032). Meanwhile, there was no distinct statistical difference between and healthy controls (P=0.690).(6) Linkage disequilibrium and haplotype analysis by SHEsis online software shows that linkage disequilibrium existed in XRCC2C41657T and G4234C SNPs (D’=0.184, r2=0.032, P=1.62e-8). Distribution of four haplotypes of XRCC2in patients was distinctly differently from that in controls (x2=11.189, P=0.011).41657C/4234G was most common haplotype. Distribution of41657T/4234C in colorectal cancer cases was7.5%, obviously higher than3.1%in healthy controls (x2=10.180, P=0.001). Unconditional Logistic-regression Analysis showed that41657T/4234C haplotype carriers had higher risk of colorectal cancer (OR=2.601,95%CI=1.421-4.758).Conclusion:(1)XRCC2C41657T polymorphism is relevant to the risk of colorectal cancer. CT and TT genotypes can distinctly increase the risk of colorectal cancer, while T allele is a risk factor of colorectal cancer. Genotypes and allele frequency of XRCC2G4234C is not of statistical significance in cases and controls, while it is not relevant to the risk of colorectal cancer.(2) XRCC2C41657T SNP are not associated to clinicopathologic features such as structure position, general type, differentiated degree, infiltration depth and lymph gland transfer and tumor histological type of CRC.(3) There is distinct difference between protein expression of XRCC2in colorectal cancer tissues and normal tissues. Expression of XRCC2protein is higher in cancer. Expression of XRCC2protein is associated to genotypes of C41657T in colorectal cancer tissue but not be in normal tissue.(4) XRCC2genotype C41657T and G4234C SNPs are in linkage disequilibrium.41657C/4234G haplotype is most common. Compared to41657C/4234G,41657T/4234C increases more risk of colorectal cancer.