Two Genetic Variants in Prostate Stem Cell Antigen and Gastric Cancer Susceptibility in a Chinese Population

Genetic factors play important roles in pathogenesis of human cancer. A recent genome-wide association study (GWAS) linked two single nucleotide polymorphisms (SNPs) in prostate stem cell antigen (PSCA), rs2294008C>T and rs2976392G>A, to risk of diffuse-type of gastric cancer in Japanese and Korean populations. We hypothesized that these two SNPs are also associated with risk of gastric cancer in Chinese population. We examined genotypes and haplotypes of PSCA, rs2294008C/T and rs2976392G/A in 716 patients with cardia gastric carcinoma (CGC), 1020 patients with noncardia gastric carcinoma (NCGC), and 1020 controls. We found that individuals with at least one copy of the rs2294008T allele (CT or TT genotype) had an elevated risk for developing NCGC compared with those without this allele (OR 1.35, 95% CI = 1.13-1.61). Individuals with at least one copy of the rs2976392A allele (GA or AA genotype) had nonsignificantly increased risk for NCGC compared with those without this allele (OR = 1.20, 95% CI = 1.01-1.43). Stratification analysis showed that the increased risk associated with the SNPs was restricted in female subjects. Moreover, the rs2294008T and rs2976392A allele carriers were predisposed to developing poorly differentiated and high stage NCGC at diagnosis. However, no such association was detected for CGC. In addition, we observed considerably lower allelic and genotype frequencies of these genetic variants in Chinese population compared with Japanese and Korean populations. These findings are in general consistent with previous GWAS and suggest that PSCA may play a role in the development of NCGC in Chinese population. (C) 2009 Wiley-Liss, Inc.