Department of Molecular and Genetic Toxicology, Cancer Center of Nanjing Medical University, Nanjing 210029, China.
Carcinogenesis. 2010 Apr;31(4):621-4. doi: 10.1093/carcin/bgp323. Epub 2010 Jan 18.
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.
最近，两项全基因组关联研究分别在亚洲人群中发现前列腺干细胞抗原（PSCA）rs2294008（C>T）多态性与弥漫型胃癌风险之间存在显著关联，在白种人群中与膀胱癌风险之间存在显著关联。PSCA 在膀胱癌中高度表达，被认为是膀胱癌诊断和进展的有用标志物。为了确定 rs2294008 多态性是否与中国人群膀胱癌的风险相关，我们进行了一项基于医院的病例对照研究，共纳入 581 例病例和 580 例对照。我们选取了 16 例肿瘤旁正常膀胱组织，用于评估该多态性的功能。我们对 rs2294008 多态性进行了基因分型，并评估了其与膀胱癌风险及正常膀胱组织中信使 RNA（mRNA）表达的相关性。与 CC 基因型相比，rs2294008 CT/TT 基因型显著增加了膀胱癌的发病风险（调整后的优势比，1.38；95%置信区间，1.09-1.75）。此外，PSCA mRNA 表达分析表明 rs2294008 与 PSCA mRNA 表达水平存在明显相关性。这些结果表明，PSCA 基因的 rs2294008 多态性可能在膀胱癌的发生发展中起作用，可作为中国人群膀胱癌遗传易感性的生物标志物。
