title: Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study.
abstract: BACKGROUND
  Patients 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.
  
  
  METHODS
  PSCA 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).
  
  
  RESULTS
  Frequency 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 (2.17 ± 0.75) was significantly lower than that in C/C genotype (3.39 ± 1.27, p < .001).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uotani
authors.forename: Shu
authors.initials: S
authors.lastname: Sahara
authors.forename: Mihoko
authors.initials: M
authors.lastname: Yamade
authors.forename: Moriya
authors.initials: M
authors.lastname: Iwaizumi
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Osawa
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D044466:Asian People; D001284:Atrophy / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005753:Gastric Mucosa / Q000473:pathology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010437:Peptic Ulcer / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human
keywords: H. pylori; PSCA; duodenal ulcer; dupA; gastric cancer