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

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

Author information

  • 1Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland.

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.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID:
21070776
[PubMed - indexed for MEDLINE]
PMCID:
PMC3031760
Free PMC Article
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