Influence of Prostate Stem Cell Antigen Gene Polymorphisms on Susceptibility to Helicobacter pylori-associated Diseases: A Case-control Study

BackgroundPatients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H.pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy. MethodsPSCA rs2294008 C>T polymorphism was assessed in H.pylori-positive Japanese patients (n=488) with noncardia gastric cancer (n=193), gastric ulcer (n=84), duodenal ulcer (n=61), and atrophic gastritis (n=150), as well as in H.pylori-negatives (n=266). ResultsFrequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H.pylori-negatives (19.5%) (p<.001). Compared with duodenal ulcer, having the T allele significantly increased the risk of gastric cancer (OR: 3.97, 95% CI: 2.02-7.80; p<.001), gastric ulcer (2.40, 1.13-5.10; p=.023), and gastritis (4.72, 2.26-9.86; p<.001). Mean pepsinogen (PG) I/PG II ratio in T allele carriers (2.170.75) was significantly lower than that in C/C genotype (3.39 +/- 1.27, p<.001). ConclusionsThe PSCA rs2294008 C>T polymorphism is associated with differing susceptibilities to H.pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer.