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Recently, two genome-wide association studies identified a significant association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and risk of diffuse-type of gastric cancer in Asians and bladder cancer in Caucasians, respectively. PSCA has been reported highly expressed in bladder cancer and been considered as a useful marker for diagnosis and progression of bladder cancer. To determine whether rs2294008 polymorphism is associated with risk of bladder cancer in Chinese populations, we conducted a hospital-based case–control study of 581 cases and 580 controls. Sixteen normal bladder tissues adjacent to tumors were used to evaluate the functionality of this polymorphism. We genotyped the rs2294008 polymorphism and assessed its association with risk of bladder cancer and messenger RNA (mRNA) expression in normal bladder tissues. A significant increased risk of bladder cancer was found for rs2294008 CT/TT genotypes (adjusted odds ratio, 1.38; 95% confidence interval, 1.09–1.75) compared with the CC genotype. Furthermore, analysis of PSCA mRNA expression identified a clear correlation of rs2294008 with expression levels of PSCA mRNA. These results indicated that the rs2294008 polymorphism of PSCA gene may play a role in bladder cancer carcinogenesis and it could be served as a biomarker for genetic susceptibility to bladder cancer in Chinese populations. [ABSTRACT FROM PUBLISHER]

Transforming growth factor-β (TGF-β) is a multifunctional growth factor that plays important roles in many biological processes, whereas RUNX3 is a target of TGF-β-mediated tumor suppressor pathway. In humans, RUNX3 inactivation may lead to the cancer development, including bladder cancer. To determine whether the RUNX3 polymorphisms are associated with risk of bladder cancer, we conducted a case–control study of 368 bladder cancer patients and 368 cancer-free controls to assess the associations between the RUNX3 tagging single-nucleotide polymorphisms (tSNPs) and bladder cancer risk. In the single-locus analysis, we found a significantly increased risk of bladder cancer associated with the SNP7 rs760805 AA genotype (adjusted odds ratio = 1.97, 95% confidence interval = 1.44–2.69), compared with the AT/TT genotype. Haplotype-based association analysis revealed that the increased risk of bladder cancer was significantly associated with two haplotypes TATCCCAAAA (2.37, 1.16–4.83) and AGCTTGAGAG (2.70, 1.08–6.72) that included the rs760805 A allele. Multifactor dimensionality reduction (MDR) analysis identified a significant more than multiplicative interaction between the SNP7 rs760805 AA and smoking and an additive interaction between the SNP3 rs11249206 TT and smoking on bladder cancer risk. The SNP3 rs11249206, SNP5 rs1395621, SNP7 rs760805, SNP8 rs2236852 and the trichotomized cumulative smoking were the five factors best predicted by the MDR models. When the variables were combined and dichotomized and fitted into the MDR model, the subjects carrying the combined risk stratum had a significantly increased risk for bladder cancer (6.37, 4.57–8.87, P = 7.03 × 10−28). These results suggested that the genetic variants in RUNX3 may modulate the risk of bladder cancer. [ABSTRACT FROM AUTHOR]