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

Paul Lochhead, Bernd Frank, Georgina L. Hold, Charles S. Rabkin, Michael T. H. Ng, Thomas L. Vaughan, Harvey A. Risch, Marilie D. Gammon, Jolanta Lissowska, Melanie N. Weck, Elke Raum, Heiko Müller, Thomas Illig, Norman Klopp, Alan Dawson, Kenneth E. McColl, Hermann Brenner, Wong-Ho Chow, Emad M. El-Omar

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Pages (from-to)435-441
Number of pages7
JournalGastroenterology
Volume140
Issue number2
Early online date9 Nov 2010
DOIs
Publication statusPublished - Feb 2011

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Gastrointestinal Neoplasms
Stomach Neoplasms
Prostate
Stem Cells
Odds Ratio
Antigens
Confidence Intervals
Genes
Atrophic Gastritis
Alleles
Achlorhydria
Population
Cardia
Confounding Factors (Epidemiology)
Population Control
Pylorus
Esophageal Neoplasms
Helicobacter pylori
Atrophy
Case-Control Studies

Keywords

  • stomach cancer
  • esophageal cancer
  • genetic polymorphisms
  • cancer genetics

Cite this

Lochhead, P., Frank, B., Hold, G. L., Rabkin, C. S., Ng, M. T. H., Vaughan, T. L., ... El-Omar, E. M. (2011). Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals. Gastroenterology, 140(2), 435-441. https://doi.org/10.1053/j.gastro.2010.11.001

Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals. / Lochhead, Paul; Frank, Bernd; Hold, Georgina L.; Rabkin, Charles S.; Ng, Michael T. H.; Vaughan, Thomas L.; Risch, Harvey A.; Gammon, Marilie D.; Lissowska, Jolanta; Weck, Melanie N.; Raum, Elke; Müller, Heiko; Illig, Thomas; Klopp, Norman; Dawson, Alan; McColl, Kenneth E.; Brenner, Hermann; Chow, Wong-Ho; El-Omar, Emad M.

In: Gastroenterology, Vol. 140, No. 2, 02.2011, p. 435-441.

Research output: Contribution to journalArticle

Lochhead, P, Frank, B, Hold, GL, Rabkin, CS, Ng, MTH, Vaughan, TL, Risch, HA, Gammon, MD, Lissowska, J, Weck, MN, Raum, E, Müller, H, Illig, T, Klopp, N, Dawson, A, McColl, KE, Brenner, H, Chow, W-H & El-Omar, EM 2011, 'Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals', Gastroenterology, vol. 140, no. 2, pp. 435-441. https://doi.org/10.1053/j.gastro.2010.11.001
Lochhead, Paul ; Frank, Bernd ; Hold, Georgina L. ; Rabkin, Charles S. ; Ng, Michael T. H. ; Vaughan, Thomas L. ; Risch, Harvey A. ; Gammon, Marilie D. ; Lissowska, Jolanta ; Weck, Melanie N. ; Raum, Elke ; Müller, Heiko ; Illig, Thomas ; Klopp, Norman ; Dawson, Alan ; McColl, Kenneth E. ; Brenner, Hermann ; Chow, Wong-Ho ; El-Omar, Emad M. / Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals. In: Gastroenterology. 2011 ; Vol. 140, No. 2. pp. 435-441.
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T1 - Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals

AU - Lochhead, Paul

AU - Frank, Bernd

AU - Hold, Georgina L.

AU - Rabkin, Charles S.

AU - Ng, Michael T. H.

AU - Vaughan, Thomas L.

AU - Risch, Harvey A.

AU - Gammon, Marilie D.

AU - Lissowska, Jolanta

AU - Weck, Melanie N.

AU - Raum, Elke

AU - Müller, Heiko

AU - Illig, Thomas

AU - Klopp, Norman

AU - Dawson, Alan

AU - McColl, Kenneth E.

AU - Brenner, Hermann

AU - Chow, Wong-Ho

AU - El-Omar, Emad M.

N1 - Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2011/2

Y1 - 2011/2

N2 - Background & AimsAn 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.MethodsWe 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.ResultsCarriage 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).ConclusionsThe rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.

AB - Background & AimsAn 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.MethodsWe 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.ResultsCarriage 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).ConclusionsThe rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.

KW - stomach cancer

KW - esophageal cancer

KW - genetic polymorphisms

KW - cancer genetics

U2 - 10.1053/j.gastro.2010.11.001

DO - 10.1053/j.gastro.2010.11.001

M3 - Article

VL - 140

SP - 435

EP - 441

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 2

ER -