Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-amino acid protein related to the cell proliferation inhibition and/or cell death induction activity which has attracted considerable attention as a candidate gene for gastric cancer (GC) since it was first identified through genome-wide association approach. Since then, the relationship between PSCA polymorphisms (rs2294008, rs2976392) and GC has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 16 studies involving a total of 18,820 cases and 35,756 controls for the two widely studied polymorphisms of PSCA on genetic susceptibility for GC. Overall, the summary odds ratio for GC was 1.46 (95% CI 1.30-1.69, P < 10(-5)) and 1.49 (95% CI 1.22-1.82, P < 10(-4)) for PSCA rs2294008 and rs2976392 polymorphisms, respectively. Meanwhile, haplotype analyses of the two polymorphisms revealed a significant association between the combination of these alleles and GC risk. When stratifying for ethnicity, significantly increased risks were found for rs2294008 and rs2976392 polymorphism among East Asians in all genetic models, while no significant associations were observed for the rs2294008 polymorphism in Caucasians. In the stratified analyses according to histological type, and source of controls, evidence of gene-disease association was still obtained. In addition, our data indicate that rs2294008 of PSCA is involved in GC susceptibility and confer its effect primarily in noncardia tumors (OR = 1.30, 95% CI 1.12-1.53, P < 10(-4)). Our findings demonstrated that rs2294008 and rs2976392 polymorphism of PSCA is a risk-conferring factor associated with increased GC susceptibility, especially in East Asians.