Association Of Genetic Polymorphism Of CCNE1and RIP2with Bladder Cancer Risk

ObjectiveAlleles at single nucleotide polymorphisms (SNPs) rs8102137and rs42490within the5’-UTR of CCNE1and the intron of RIP2, respectively, had an uncertain impact on cancer risk. Here, we want to identify the relationship of these two SNPs with Bladder Transitional Cell Carcinoma risk.Materials and MethodsThe study included176patients with BTCC (Bladder Transitional Cell Carcinoma), The control group comprised210healthy blood donors who had a medical examination. A total of5ml of peripheral venous blood was drawn with EDTA as an anticoagulant. And total genomic DNA was isolated from peripheral blood. Detection of genotype variants was analyzed by the polymerase chain reaction-restriction sequencing method. The diagnoses, pathological grade and stage of bladder cancer were all determined according to the pathological reports of transurethral bladder cancer resection, partial cystectomy and radical cystectomy. Hardy-Weinberg equilibrium was checked in control by the goodness of fit χ2test. Genotype and allele frequencies of the CCNE1and RIP2gene in the healthy group and in the bladder cancer group were analyzed using the χ2test. The relationship between polymorphisms and the risk to bladder cancer were analyzed using the odds ratio (OR) and95%confidence intervals (CI). Statistical significance was set at P<0.05. The SPSS version13.0software package was used for analyzes.Results1. The detection of CCNE1and RIP2genetic equilibrium The frequencies of rs8102103and rs42490locus conform to Hardy-Weinberg equilibrium, insuring the reliability of their application to evaluate larger groups.2. Association between CCNEl(rs8102137) genotypes or alleles andsusceptibility of bladder cancerIn patients, the frequencies of the T/T, T/C and C/C genotypes were59.09%(104/176).39.20%(69/176)、1.70%(3/176), respectively. In controls, the frequencies of the T/T, T/C and C/C genotypes were69.05%(145/210)、 29.52%(62/210)、1.43%(3/210), respectively. The frequency of CCNE1(rs8102137) variant allele was significantly higher in patients (40.91%) than in controls (30.95%)(P<0.05, OR=1.54,95%CI1.02-2.45).3. Association between RIP2(rs42490) genotypes or alleles and susceptibility of bladder cancerIn patients, the frequencies of the T/T, T/C and C/C genotypes were27.27%(48/176)、46.02%(81/176)、26.70%(47/176), respectively. In controls, the frequencies of the T/T, T/C and C/C genotypes were37.62%(79/210)、45.71%(96/210)、16.67%(35/210), respectively. The frequency of CCNE1(rs8102137) variant allele was significantly higher inpatients (72.73%) than in controls (62.38%)(P<0.05, OR=1.61,95%CI1.04-2.48).4. CCNE1and RIP2genotypes and pathological grade and clinical stage of bladder cancerFor the CCNE1(rs8102137) and RIP2(rs42490) genotypes, there was no association between the CCNE1(rs8102137) and RIP2(rs42490) Polymorphisms and Pathological grade and clinical stage of bladder cancer. We did not found significant association between the studied polymorphisms with neither tumor grade nor tumor stage.Conclusions1. The genotype T/C and C/C in CCNE1rs8102137showed an increased cancer risk when compared with T carriers in our study population; The genotype G/A and A/A in RIP2rs42490showed an increased cancer risk when compared with G carriers in our study population.2. No significant association between the studied polymorphisms with neither tumor grade nor tumor stage.