Genetic Variation in the Prostate Stem Cell Antigen Gene and Upper Gastrointestinal Cancer in White Individuals
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. We genotyped 166 relatives of gastric cancer...
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| Published in | Gastroenterology (New York, N.Y. 1943) Vol. 140; no. 2; pp. 435 - 441 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.02.2011
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| Subjects | |
| Online Access | Get full text |
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| Abstract | 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.
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.
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).
The rs2294008 polymorphism in
PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers. |
|---|---|
| AbstractList | 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.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.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.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.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).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).The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.CONCLUSIONSThe rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers. 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. 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. 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). The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers. 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. 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. 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). The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers. 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. |
| Author | Risch, Harvey A. Chow, Wong–Ho Vaughan, Thomas L. Raum, Elke Ng, Michael T.H. Dawson, Alan Weck, Melanie N. Hold, Georgina L. Brenner, Hermann Illig, Thomas Gammon, Marilie D. El–Omar, Emad M. Lissowska, Jolanta McColl, Kenneth E. Müller, Heiko Lochhead, Paul Frank, Bernd Rabkin, Charles S. Klopp, Norman |
| Author_xml | – sequence: 1 givenname: Paul surname: Lochhead fullname: Lochhead, Paul organization: Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland – sequence: 2 givenname: Bernd surname: Frank fullname: Frank, Bernd organization: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany – sequence: 3 givenname: Georgina L. surname: Hold fullname: Hold, Georgina L. organization: Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland – sequence: 4 givenname: Charles S. surname: Rabkin fullname: Rabkin, Charles S. organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland – sequence: 5 givenname: Michael T.H. surname: Ng fullname: Ng, Michael T.H. organization: Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland – sequence: 6 givenname: Thomas L. surname: Vaughan fullname: Vaughan, Thomas L. organization: Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington – sequence: 7 givenname: Harvey A. surname: Risch fullname: Risch, Harvey A. organization: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut – sequence: 8 givenname: Marilie D. surname: Gammon fullname: Gammon, Marilie D. organization: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina – sequence: 9 givenname: Jolanta surname: Lissowska fullname: Lissowska, Jolanta organization: Division of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland – sequence: 10 givenname: Melanie N. surname: Weck fullname: Weck, Melanie N. organization: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany – sequence: 11 givenname: Elke surname: Raum fullname: Raum, Elke organization: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany – sequence: 12 givenname: Heiko surname: Müller fullname: Müller, Heiko organization: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany – sequence: 13 givenname: Thomas surname: Illig fullname: Illig, Thomas organization: Institute of Epidemiology, Research Centre for Environment and Health, Neuherberg, Germany – sequence: 14 givenname: Norman surname: Klopp fullname: Klopp, Norman organization: Institute of Epidemiology, Research Centre for Environment and Health, Neuherberg, Germany – sequence: 15 givenname: Alan surname: Dawson fullname: Dawson, Alan organization: Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland – sequence: 16 givenname: Kenneth E. surname: McColl fullname: McColl, Kenneth E. organization: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland – sequence: 17 givenname: Hermann surname: Brenner fullname: Brenner, Hermann organization: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany – sequence: 18 givenname: Wong–Ho surname: Chow fullname: Chow, Wong–Ho organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland – sequence: 19 givenname: Emad M. surname: El–Omar fullname: El–Omar, Emad M. email: e.el-omar@abdn.ac.uk organization: Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21070776$$D View this record in MEDLINE/PubMed |
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| Copyright | 2011 AGA Institute AGA Institute Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. |
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| Keywords | Stomach Cancer GWAS IL OR PSCA CI EAC CAG Cancer Genetics ESCC Genetic Polymorphisms SNP HWE Esophageal Cancer α7-nAChRs single nucleotide polymorphism odds ratio Hardy–Weinberg equilibrium prostate stem cell antigen genome wide association study interleukin esophageal squamous cell carcinoma α7 subunit-containing nicotinic acetylcholine receptors chronic atrophic gastritis esophageal adenocarcinoma confidence interval |
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| Snippet | 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... Background & Aims An association between gastric cancer and the rs2294008 (C>T) polymorphism in the prostate stem cell antigen ( PSCA ) gene has been reported... 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... |
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| SubjectTerms | Adenocarcinoma - epidemiology Adenocarcinoma - genetics Antigens, Neoplasm - genetics Cancer Genetics Carcinoma, Squamous Cell - epidemiology Carcinoma, Squamous Cell - genetics Case-Control Studies Esophageal Cancer Esophageal Neoplasms - epidemiology Esophageal Neoplasms - genetics Female Gastritis, Atrophic - epidemiology Gastritis, Atrophic - genetics Gastroenterology and Hepatology Gastrointestinal Neoplasms - epidemiology Gastrointestinal Neoplasms - genetics Genetic Polymorphisms Genetic Predisposition to Disease GPI-Linked Proteins - genetics Helicobacter Infections - epidemiology Helicobacter Infections - genetics Helicobacter pylori - isolation & purification Humans Male Neoplasm Proteins - genetics Polymorphism, Single Nucleotide Risk Stomach Cancer White People - genetics |
| Title | Genetic Variation in the Prostate Stem Cell Antigen Gene and Upper Gastrointestinal Cancer in White Individuals |
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