Department of Molecular and Genetic Toxicology, School of Public Health, Cancer Center, Nanjing Medical University, Nanjing, China.
Int J Cancer. 2011 Sep 1;129(5):1207-13. doi: 10.1002/ijc.25740. Epub 2010 Dec 9.
Recent genome-wide association study (GWAS) has identified that the prostate stem cell antigen (PSCA) rs2294008 is involving in regulating gastric epithelial-cell proliferation, influencing the risk of diffuse-type gastric cancer. We hypothesized that PSCA rs2294008 is also associated with gastric cancer survival. We genotyped PSCA rs2294008 using TaqMan method in 943 patients with surgically resected gastric cancer. Analyses of genotype association with survival outcomes were assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. There was no significant association between rs2294008 and survival of gastric cancer (log-rank p=0.085 for CT/TT versus CC). However, in the stratification analysis of histology, we found that rs2294008 CT/TT genotypes were associated with significantly improved survival among diffuse-type gastric cancer (log-rank p=0.025, hazard ratio [HR]=0.75, 95% confidence interval [CI]=0.59-0.96), compared to the CC genotype. Moreover, this protective effect was more predominant for diffuse-type gastric cancer patients with tumor size >5 cm and distant metastasis. If validated in further studies, PSCA rs2294008 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the diffuse-type gastric cancer.
最近的全基因组关联研究（GWAS）已经确定前列腺干细胞抗原（PSCA）rs2294008 参与调节胃上皮细胞增殖，影响弥漫型胃癌的风险。我们假设 PSCA rs2294008 也与胃癌的生存有关。我们使用 TaqMan 方法在 943 名接受手术切除的胃癌患者中对 PSCA rs2294008 进行了基因分型。通过 Kaplan-Meier 方法、Cox 比例风险模型和对数秩检验评估基因型与生存结果的关联。rs2294008 与胃癌的生存无显著相关性（CT/TT 与 CC 相比，对数秩检验 p=0.085）。然而，在组织学的分层分析中，我们发现 rs2294008 CT/TT 基因型与弥漫型胃癌的生存显著改善相关（log-rank p=0.025，风险比 [HR]=0.75，95%置信区间 [CI]=0.59-0.96），与 CC 基因型相比。此外，这种保护作用在肿瘤大小>5cm 和远处转移的弥漫型胃癌患者中更为明显。如果在进一步的研究中得到验证，PSCA rs2294008 可能成为评估胃癌生存和个体化临床治疗的有用标志物，尤其是在弥漫型胃癌患者中。
