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Keywords:

  • PSCA;
  • GWAS;
  • gastric cancer;
  • survival;
  • molecular epidemiology

Abstract

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.