Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals

Gastroenterology. 2011 Feb;140(2):435-41. doi: 10.1053/j.gastro.2010.11.001. Epub 2010 Nov 9.

Abstract

Background & aims: An association between gastric cancer and the rs2294008 (C>T) polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals.

Methods: We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori-infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori-negative relatives, and 100 population controls. Additionally, a population-based study of chronic atrophic gastritis provided 533 cases and 1054 controls. We then genotyped 2 population-based, case-control studies of upper gastrointestinal cancer: the first included 312 gastric cancer cases and 383 controls; the second included 309 gastric cancer cases, 159 esophageal cancer cases, and 211 controls. Odds ratios were computed from logistic models and adjusted for confounding variables.

Results: Carriage of the risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1-1.9) and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3-2.8). The association was strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2-10.7). An inverse association was observed between carriage of the risk allele and gastric cardia cancer (OR, 0.5; 95% CI: 0.3-0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI: 0.3-0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2-0.9).

Conclusions: The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics*
  • Antigens, Neoplasm / genetics*
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • Esophageal Neoplasms / epidemiology
  • Esophageal Neoplasms / genetics*
  • Female
  • GPI-Linked Proteins / genetics
  • Gastritis, Atrophic / epidemiology
  • Gastritis, Atrophic / genetics
  • Gastrointestinal Neoplasms / epidemiology
  • Gastrointestinal Neoplasms / genetics*
  • Genetic Predisposition to Disease
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / genetics
  • Helicobacter pylori / isolation & purification
  • Humans
  • Male
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Risk
  • White People / genetics

Substances

  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • Neoplasm Proteins
  • PSCA protein, human