Association Of Genetic Polymorphism Of GSTM1and PSCA With Bladder Cancer Risk

ObjectiveThis research intends to evaluate the relationship between GSTM1-02polymorphism of the GSTM1gene or rs2294008polymorphism of the PSC A gene and the incidence risk, clinic stage, pathologic grading and recurrence of Bladder Urothelial Cell Carcinoma (BUCC) in Chinese Han population.MethodsIn this hospital-based case-control study conducted in Chinese Han population,358patients who were diagnosed as BUCC and434healthy normal subjects were recruited from the Second Hospital of Tianjin Medical University. Genomic DNA was extracted from peripheral blood of358bladder cancer patients and434control subjects. We used polymerase chain reaction (PCR) and allele-specific PCP (AS-PCR) for detection of genetic polymorphisms of GSTM1and PSCA, and then verified genotyping results of PSCA by sequencing method.Statistic analysisStatistical analysis was conducted using the Package SPSS20.0for Windows. Student’s t tests and chi-square (χ2) tests were used to assess differences in the distribution of age, sex and smoking history between cases and controls. Chi-square analysis was used to compare correlates between the genetic polymorphisms of GSTM1-02or rs2294008and the risk of bladder cancer in Chinese Han population. Unconditional logistic was used to calculate crude and adjusted odd ratios (OR) and their95%confidence intervals (95%CI) with and without adjustment for age, sex and smoking history. All statistical tests were2-sided and P<0.05was considered statistically significant.Results1. Association between GSTM1-02polymorphism and bladder cancer riskThe result of a chi-square test revealed that the differences in the distribution of GSTM1null genotype between the cases and controls was not statistically significant (P>0.05, adjusted OR=1.19,95%CI=0.89-1.58).2. Association between rs2294008polymorphism and bladder cancer riskStatistically significant differences were noticed in the distribution of the combined C/T and T/T genotypes between the cases and controls (P<0.05). Logistic regression analysis revealed that the combined C/T and T/T variant also had a increased risk of bladder cancer (adjusted OR=1.54,95%CI=1.15-2.06). There was a significant trend for an allele dose effect on risk of bladder cancer (Ptrend=0.001). The increased risk of bladder cancer associated with variant genotypes of rs2294008(C/T and T/T) can be observed in subgroups age (older than65years)(adjusted OR=1.80,95%CI=1.17-2.75), sex (male)(adjusted OR=1.57,95%CI=1.14-2.18), smoking status (ever)(adjusted OR=1.79,95%CI=1.15-2.80)(all the P<0.05).3. Association between GSTM1-02and rs2294008polymorphism and pathological staging or grading of bladder cancerFisher’s exact tests revealed that no statistically significant differences were found in the distribution of the variant genotypes of GSTM1and PSCA among various pathological stages and grades of bladder cancer (all the P>0.05).4. Association between GSTM1-02and rs2294008polymorphism and bladder cancer recurrenceA chi-square test showed that no statistically significant differences were noticed in the distribution of the variant genotypes of GSTM1and PSCA bettween the recurrence group and the non-recurrence group (all the P>0.05). ConclusionsThere was no association between the GSTM1-02polymorphic deletion of the GSTM1gene and genetic susceptibility to bladder cancer in Chinese Han population. The PSCA C/T and T/T variants can significantly increase the risk of bladder cancer in Chinese Han population, especially in people age>65, man and ever smoker subgroups.