title: Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma.
abstract: The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P < 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P < 10(-5) ) although not genome-wide significantly associated with the BEACON GWAS. Therefore, both variants and corresponding genes represent promising candidates for future EAC association studies on independent samples.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Becker
authors.affiliation: Department of Medicine II, Sana Klinikum, Offenbach, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: May
authors.affiliation: Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gerges
authors.affiliation: Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.|Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Kinikum, Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Anders
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Veits
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Weise
authors.affiliation: Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Darina
authors.initials: D
authors.lastname: Czamara
authors.affiliation: Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: Orestis
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authors.lastname: Lyros
authors.affiliation: Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany.
authors.forename: Hendrik
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authors.lastname: Manner
authors.affiliation: Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
authors.forename: Grischa
authors.initials: G
authors.lastname: Terheggen
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
authors.forename: Marino
authors.initials: M
authors.lastname: Venerito
authors.affiliation: Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Noder
authors.affiliation: Gastroenterologie am Burgweiher, Bonn, Germany.
authors.forename: Rupert
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authors.lastname: Mayershofer
authors.affiliation: Magen Darm Zentrum Wiener Platz, Cologne, Germany.
authors.forename: Jan-Hinnerk
authors.initials: JH
authors.lastname: Hofer
authors.affiliation: Gastroenterologische Schwerpunktpraxis, Baumholder, Germany.
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Karch
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
authors.forename: Constantin J
authors.initials: CJ
authors.lastname: Ahlbrand
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
authors.forename: Michael
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authors.lastname: Arras
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hofer
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Heilmann-Heimbach
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Sophie K M
authors.initials: SK
authors.lastname: Heinrichs
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Hess
authors.affiliation: Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kiesslich
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hölscher
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Bollschweiler
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.affiliation: First Department of Internal Medicine, University Medical Center, University of Mainz, Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.affiliation: Department of General and Visceral Surgery, Sana Klinikum, Offenbach, Germany.
authors.forename: Dietmar
authors.initials: D
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authors.affiliation: Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.|Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
authors.affiliation: Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.
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authors.lastname: Schmidt
authors.affiliation: Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.affiliation: Department of Epidemiology, University of Washington, School of Public Health, Seattle, Washington.|Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Gastropraxis, Wiesbaden, Germany.
authors.forename: Andreas
authors.initials: A
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authors.affiliation: Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.|Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schumacher
authors.affiliation: Department of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pech
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Vashist
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.affiliation: Gastroenterologische Gemeinschaftspraxis, Koblenz, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Weismüller
authors.affiliation: Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Neuhaus
authors.affiliation: Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rösch
authors.affiliation: Department of Medicine II, Sana Klinikum, Offenbach, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ell
authors.affiliation: Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.|Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Gockel
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C490667:BARX1 protein, human; C098521:FOXF1 protein, human; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors
keywords: BARX1; FOXF1; FOXP1; esophageal adenocarcinoma; genetic association study