title: The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk.
abstract: Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence.
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.|Departments of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Kinikum, Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Anders
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Veits
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
authors.initials: R
authors.lastname: Mayershofer
authors.affiliation: Department of Visceral Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kreuser
authors.affiliation: Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Manner
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: Magen Darm Zentrum Wiener Platz, Cologne, Germany.
authors.forename: Jan-Hinnerk
authors.initials: JH
authors.lastname: Hofer
authors.affiliation: Department of Visceral Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: Orestis
authors.initials: O
authors.lastname: Lyros
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
authors.initials: M
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: 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: Katharina
authors.initials: K
authors.lastname: Weise
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: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Böhmer
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Kosiol
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: Departments of General and Visceral Surgery, Sana Klinikum, Offenbach, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Lorenz
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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
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
authors.lastname: Hackelsberger
authors.affiliation: Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.|Departments of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schumacher
authors.affiliation: Departments 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: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
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.
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 / Q000235:genetics*; D001471:Barrett Esophagus / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D055412:Growth Differentiation Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics*; D012307:Risk Factors; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D019485:Bone Morphogenetic Proteins; C499470:GDF7 protein, human; D055412:Growth Differentiation Factors; D009363:Neoplasm Proteins; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5
keywords: ALDH1A2; Esophageal adenocarcinoma; GDF7; TBX5; genetic association study