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Grant Details

Grant Number: 5R03CA110822-02 Interpret this number
Primary Investigator: Liu, Geoffrey
Organization: Massachusetts General Hospital
Project Title: H.pylori, Genes and Esophageal Adenocarcinoma
Fiscal Year: 2005
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Abstract

DESCRIPTION (provided by applicant): Esophageal adenocarcinoma (EA) has the fastest rising incidence of all cancers in the United States. The overall annual incidence has more than tripled over a twenty year period. These statistics imply an urgent problem that needs addressing, and an environmental component to the etiology and pathogenesis of EA. Although gastroesophageal reflux disease, Barrett's esophagus and obesity are known risk factors for EA, more recently, a protective effect for Helicobacter pylori (HP) has been hypothesized based on the results of several studies. One objective of this research is to confirm earlier results in a large sample of over 250 histologically-confirmed incident EA cases. Through a secondary analysis of data and specimens from two separate molecular epidemiologic studies, the association between Helicobacter pylori and EA risk will be examined via a case-control design, after taking into account important covariates such as gastroesophageal reflux, Barrett's esophagus, and body-mass index. In addition, there may be host factors such as genetic polymorphisms that modify the relationship between HP and EA risk. Genetic polymorphisms involved in three pathways will be evaluated as potential modifiers of this relationship: (a) genes in the inflammatory pathway, such as IL1-beta; (b) genes involved in free radical formation such as MPO and MnSOD; and (c) several candidate DNA repair genes. Both single nucleotide polymorphisms and haplotypes will be evaluated as potential modifiers of the HP-EA risk association. One long-term goal of this small grant project is to generate information that will ultimately lead to a more comprehensive large scale population-based case-control study of EA risks. This application addresses directly priorities set by the NCl, in particular, the recommendations of the Stomach and Esophageal Cancer Progress Report Group (2002), and may have important impact on current medical practices related to the aggressiveness of treating HP infections.

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Publications

Single nucleotide polymorphisms in the matrix metalloproteinase gene family and the frequency and duration of gastroesophageal reflux disease influence the risk of esophageal adenocarcinoma.
Authors: Cheung W.Y. , Zhai R. , Bradbury P. , Hopkins J. , Kulke M.H. , Heist R.S. , Asomaning K. , Ma C. , Xu W. , Wang Z. , et al. .
Source: International journal of cancer, 2012-12-01; 131(11), p. 2478-86.
EPub date: 2012-04-24.
PMID: 22422400
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Interactions between environmental factors and polymorphisms in angiogenesis pathway genes in esophageal adenocarcinoma risk: a case-only study.
Authors: Zhai R. , Zhao Y. , Liu G. , Ter-Minassian M. , Wu I.C. , Wang Z. , Su L. , Asomaning K. , Chen F. , Kulke M.H. , et al. .
Source: Cancer, 2012-02-01; 118(3), p. 804-11.
EPub date: 2011-07-12.
PMID: 21751195
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Genome-wide DNA methylation profiling of cell-free serum DNA in esophageal adenocarcinoma and Barrett esophagus.
Authors: Zhai R. , Zhao Y. , Su L. , Cassidy L. , Liu G. , Christiani D.C. .
Source: Neoplasia (New York, N.Y.), 2012 Jan; 14(1), p. 29-33.
PMID: 22355271
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Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma.
Authors: Wu I.C. , Zhao Y. , Zhai R. , Liu G. , Ter-Minassian M. , Asomaning K. , Su L. , Liu C.Y. , Chen F. , Kulke M.H. , et al. .
Source: Neoplasia (New York, N.Y.), 2011 Apr; 13(4), p. 386-92.
PMID: 21472143
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A Large-scale genetic association study of esophageal adenocarcinoma risk.
Authors: Liu C.Y. , Wu M.C. , Chen F. , Ter-Minassian M. , Asomaning K. , Zhai R. , Wang Z. , Su L. , Heist R.S. , Kulke M.H. , et al. .
Source: Carcinogenesis, 2010 Jul; 31(7), p. 1259-63.
EPub date: 2010-05-07.
PMID: 20453000
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Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma.
Authors: Zhai R. , Chen F. , Liu G. , Su L. , Kulke M.H. , Asomaning K. , Lin X. , Heist R.S. , Nishioka N.S. , Sheu C.C. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2010-05-10; 28(14), p. 2445-51.
EPub date: 2010-04-12.
PMID: 20385987
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Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk.
Authors: Cheung W.Y. , Zhai R. , Kulke M.H. , Heist R.S. , Asomaning K. , Ma C. , Wang Z. , Su L. , Lanuti M. , Tanabe K.K. , et al. .
Source: Carcinogenesis, 2009 Aug; 30(8), p. 1363-7.
EPub date: 2009-06-11.
PMID: 19520791
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Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis.
Authors: Bradbury P.A. , Zhai R. , Ma C. , Xu W. , Hopkins J. , Kulke M.J. , Asomaning K. , Wang Z. , Su L. , Heist R.S. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2009-07-15; 15(14), p. 4680-5.
EPub date: 2009-07-07.
PMID: 19584152
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MDM2 promoter polymorphism and pancreatic cancer risk and prognosis.
Authors: Asomaning K. , Reid A.E. , Zhou W. , Heist R.S. , Zhai R. , Su L. , Kwak E.L. , Blaszkowsky L. , Zhu A.X. , Ryan D.P. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2008-06-15; 14(12), p. 4010-5.
PMID: 18559624
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A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome.
Authors: Lanuti M. , Liu G. , Goodwin J.M. , Zhai R. , Fuchs B.C. , Asomaning K. , Su L. , Nishioka N.S. , Tanabe K.K. , Christiani D.C. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2008-05-15; 14(10), p. 3216-22.
PMID: 18483390
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Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib.
Authors: Liu G. , Gurubhagavatula S. , Zhou W. , Wang Z. , Yeap B.Y. , Asomaning K. , Su L. , Heist R. , Lynch T.J. , Christiani D.C. .
Source: The pharmacogenomics journal, 2008 Apr; 8(2), p. 129-38.
EPub date: 2007-03-20.
PMID: 17375033
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Genetic polymorphisms and head and neck cancer outcomes: a review.
Authors: Hopkins J. , Cescon D.W. , Tse D. , Bradbury P. , Xu W. , Ma C. , Wheatley-Price P. , Waldron J. , Goldstein D. , Meyer F. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Mar; 17(3), p. 490-9.
PMID: 18349267
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Polymorphisms of inflammatory and metalloproteinase genes, Helicobacter pylori infection and the risk of oesophageal adenocarcinoma.
Authors: Früh M. , Zhou W. , Zhai R. , Su L. , Heist R.S. , Wain J.C. , Nishioka N.S. , Lynch T.J. , Shepherd F.A. , Christiani D.C. , et al. .
Source: British journal of cancer, 2008-02-26; 98(4), p. 689-92.
EPub date: 2008-02-05.
PMID: 18253117
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XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk.
Authors: Liu G. , Zhou W. , Yeap B.Y. , Su L. , Wain J.C. , Poneros J.M. , Nishioka N.S. , Lynch T.J. , Christiani D.C. .
Source: Carcinogenesis, 2007 Jun; 28(6), p. 1254-8.
EPub date: 2007-01-29.
PMID: 17264068
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