Relationship Between Genetic Polymorphism Of Multidrug Resistance 1 Gene And Risk Of Bladder Cancer

Objective:To validate the relationship between genetic polymorphism(rs3842?rs2032582?rs3213619) of the multidrug resistance 1(MDR1) gene and the risk of bladder cancer.Also we investigated the potential correlation between the SNPs with cancer grade/stage. Materials and Methods:A total of 545 pantients with bladder were recruited from the second Hospital of Tianjin Medical University.As control group, 649 sex- and age-matched healthy subjects without previous history of cancer were enrolled during the same period of time. All the participants are Chinese Han descent and the pantients were newly diagnosed histologically transitional cell carcinoma of bladder. Statistical analysis:Differences between cases and controls in demographic characteristics, risk factors and frequencies of allele and genotype of each SNP were evaluated by two sided ?2 test(for categorical variables) or Student's t-test(for continuous variables).Hardy–Weinberg equilibrium was evaluated by a goodness-of-?2 test to compare the observed genotype frequencies with the expected ones of the controls. Unconditional multivariate logistic regression was applied to calculate odds ratios(ORs) and 95% confidence intervals(CIs) to estimate the association between the polymorphisms and susceptibility of bladder cancer, with adjustment for age, sex and smoking status. The heterogeneity between ORs of subgroups was estimated using the ?2-based Q-test. All analyses were performed using SPSS(version 13.0) and all tests were two sided, P<0.05 was considered significant. Results: 1. Characteristics of the study participantsThere were no significant differences in distribution of age or sex between cases and controls. However,the cases had significantly higer percentage of smokers than the controls(P<0.0001). The genotype frequencies of rs3842?rs2032582?rs3213619 in controls were consistent with those expected from the Hardy-Weinberg equilibrium model(P>0.05). 2. Association between rs3842 polymorphism and bladder cancer suscepticantlyCompared to the AA genotype of rs3842, the AG/GG genotype was associated with an increased risk of bladder cancer(adjusted OR=1.28,95%CI=1.02-1.62,P=0.035).In case and control,the G allele did not implicated a significantly difference(P=0.171). 3. Association between rs3842 polymorphism and tumor grade/stageWe further analyzed the relationship between rs3842 polymorphism and tumor grade /stage for bladder cancer cases. No heterogeneity in ORs exists between tumor grades or stages(P=0.644, for High grade versus Low grade; P=0.421, for NMIBC versus MIBC), suggesting that rs9642880 polymorphism is not associated with tumor grades or stages in the study population. 4. Association between rs2032582 polymorphism and bladder cancer suscepticantlyThe T/A allel of rs2032582 in case and control did not increase risk for bladder cancer susceptibility(P=0.409,P=0.398). When the GG genotype was taken as a reference,we found that the GA genotype increased risk of bladder cancer(adjusted OR=1.56,95%CI=1.02-2.36,P=0.038) 5. Association between rs2032582 polymorphism and tumor grade/stageSimilar to the case of rs2032582, in grade/stage-stratified analysis, the SNP rs2032582 was not associated with tumor grade/stage of bladder cancer in the study population(P=0.335, for High grade versus Low grade; P=0.333, for NMIBC versus MIBC). 6. Association between rs3213619 polymorphism and tumor grade/stageThe C allel of rs3213619 was found to be associated with higher risk of bladder cancer(adjusted OR=1.47,95%CI=1.02-1.96,P=0.024) compared to the T allel. We used TT genotype as reference to analyze rs3213619 and found that the TC/CC genotype was associated with an increased risk of bladder cancer(adjusted OR=1.89,95%CI=0.98-2.47,P=0.010). 7. Association between rs3213619 polymorphism and tumor grade/stageNo heterogeneity in ORs exists between tumor grades or stages(P=0.346,for High grade versus Low grade;P=0.476,for NMIBC versus MIBC),suggesting that rs3213619 polymorphism is not associated with tumor grades or stages in the study population. But compared to the TT genotype of rs3213619, the TC/CC genotype implicated a significantly increased risk for low grade or NMIBC bladder cancer susceptibility(P=0.012, adjusted OR=1.56,95%CI=0.94-1.78; P=0.026, adjusted OR=1.30,95%CI=0.96-1.69). Conclusions:The rs3842?rs2032582 and rs3213619 genetic polymorphisms of the multidrug resistance 1(MDR1) gene are associated with risk of bladder cancer in Chinese Han population, and there is no significant association between rs3842?rs2032582? rs3213619 and tumor stage/grade in this population.