Impact of PSCA Polymorphisms on the Risk of Duodenal Ulcer

J Epidemiol. 2021 Jan 5;31(1):12-20. doi: 10.2188/jea.JE20190184. Epub 2019 Dec 14.

Abstract

Background: While duodenal ulcer (DU) and gastric cancer (GC) are both H. pylori infection-related diseases, individuals with DU are known to have lower risk for GC. Many epidemiological studies have identified the PSCA rs2294008 T-allele as a risk factor of GC, while others have found an association between the rs2294008 C-allele and risk of DU and gastric ulcer (GU). Following these initial reports, however, few studies have since validated these associations. Here, we aimed to validate the association between variations in PSCA and the risk of DU/GU and evaluate its interaction with environmental factors in a Japanese population.

Methods: Six PSCA SNPs were genotyped in 584 DU cases, 925 GU cases, and 8,105 controls from the Japan Multi-Institutional Collaborative Cohort (J-MICC). Unconditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the SNPs and risk of DU/GU.

Results: PSCA rs2294008 C-allele was associated with per allele OR of 1.34 (95% CI, 1.18-1.51; P = 2.28 × 10-6) for the risk of DU. This association was independent of age, sex, study site, smoking habit, drinking habit, and H. pylori status. On the other hand, we did not observe an association between the risk of GU and PSCA SNPs.

Conclusions: Our study confirms an association between the PSCA rs2294008 C-allele and the risk of DU in a Japanese population.

Keywords: Japan; PSCA; cross-sectional study; duodenal ulcer.

MeSH terms

  • Adult
  • Antigens, Neoplasm
  • Cohort Studies
  • Cross-Sectional Studies
  • DNA, Neoplasm / metabolism
  • Duodenal Ulcer / epidemiology
  • Duodenal Ulcer / genetics*
  • Duodenal Ulcer / microbiology
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Helicobacter Infections / complications
  • Helicobacter Infections / epidemiology
  • Helicobacter pylori
  • Humans
  • Immunoglobulin G / blood
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors

Substances

  • Antigens, Neoplasm
  • DNA, Neoplasm
  • GPI-Linked Proteins
  • Genetic Markers
  • Immunoglobulin G
  • Neoplasm Proteins
  • PSCA protein, human