The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk

Jessica Becker; Andrea May; Christian Gerges; Mario Anders; Claudia Schmidt; Lothar Veits; Tania Noder; Rupert Mayershofer; Nicole Kreuser; Hendrik Manner; Marino Venerito; Jan-Hinnerk Hofer; Orestis Lyros; Constantin J Ahlbrand; Michael Arras; Sebastian Hofer; Sophie K M Heinrichs; Katharina Weise; Timo Hess; Anne C Böhmer; Nils Kosiol; Ralf Kiesslich; Jakob R Izbicki; Arnulf H Hölscher; Elfriede Bollschweiler; Peter Malfertheiner; Hauke Lang; Markus Moehler; Dietmar Lorenz; Katja Ott; Thomas Schmidt; Markus M Nöthen; Andreas Hackelsberger; Brigitte Schumacher; Oliver Pech; Yogesh Vashist; Michael Vieth; Josef Weismüller; Michael Knapp; Horst Neuhaus; Thomas Rösch; Christian Ell; Ines Gockel; Johannes Schumacher

doi:10.1002/cam4.641

The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk

Cancer Med. 2016 May;5(5):888-91. doi: 10.1002/cam4.641. Epub 2016 Jan 18.

Authors

Jessica Becker^{1

2}, Andrea May³, Christian Gerges⁴, Mario Anders^{5

6}, Claudia Schmidt⁷, Lothar Veits⁸, Tania Noder⁵, Rupert Mayershofer⁹, Nicole Kreuser¹⁰, Hendrik Manner¹¹, Marino Venerito¹², Jan-Hinnerk Hofer¹³, Orestis Lyros¹⁰, Constantin J Ahlbrand¹⁴, Michael Arras¹⁴, Sebastian Hofer¹⁴, Sophie K M Heinrichs^{1

2}, Katharina Weise^{1

2}, Timo Hess^{1

2}, Anne C Böhmer^{1

2}, Nils Kosiol^{1

2}, Ralf Kiesslich¹¹, Jakob R Izbicki¹⁵, Arnulf H Hölscher⁷, Elfriede Bollschweiler⁷, Peter Malfertheiner¹², Hauke Lang¹⁴, Markus Moehler¹⁶, Dietmar Lorenz¹⁷, Katja Ott^{18

19}, Thomas Schmidt¹⁹, Markus M Nöthen^{1

2}, Andreas Hackelsberger²⁰, Brigitte Schumacher^{4

21}, Oliver Pech²², Yogesh Vashist¹⁵, Michael Vieth⁸, Josef Weismüller²³, Michael Knapp²⁴, Horst Neuhaus⁴, Thomas Rösch⁵, Christian Ell³, Ines Gockel¹⁰, Johannes Schumacher^{1

2}

Affiliations

¹ Institute of Human Genetics, University of Bonn, Bonn, Germany.
² Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
³ Department of Medicine II, Sana Klinikum, Offenbach, Germany.
⁴ Department of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
⁵ Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁶ Departments of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Kinikum, Berlin, Germany.
⁷ Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
⁸ Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
⁹ Gastroenterologie am Burgweiher, Bonn, Germany.
¹⁰ Department of Visceral Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
¹¹ Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany.
¹² Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
¹³ Magen Darm Zentrum Wiener Platz, Cologne, Germany.
¹⁴ Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
¹⁵ Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
¹⁶ First Department of Internal Medicine, University Medical Center, University of Mainz, Mainz, Germany.
¹⁷ Departments of General and Visceral Surgery, Sana Klinikum, Offenbach, Germany.
¹⁸ Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
¹⁹ Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.
²⁰ Gastropraxis, Wiesbaden, Germany.
²¹ Departments of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
²² Departments of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany.
²³ Gastroenterologische Gemeinschaftspraxis, Koblenz, Germany.
²⁴ Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.

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.

Keywords: ALDH1A2; Esophageal adenocarcinoma; GDF7; TBX5; genetic association study.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics*
Barrett Esophagus / genetics*
Bone Morphogenetic Proteins / genetics*
Case-Control Studies
Disease Progression
Esophageal Neoplasms / genetics*
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Growth Differentiation Factors / genetics*
Humans
Male
Neoplasm Proteins / genetics
Polymorphism, Single Nucleotide
Precancerous Conditions / genetics*
Risk Factors
T-Box Domain Proteins / genetics*

Substances

Bone Morphogenetic Proteins
GDF7 protein, human
Growth Differentiation Factors
Neoplasm Proteins
T-Box Domain Proteins
T-box transcription factor 5

Supplementary concepts

Adenocarcinoma Of Esophagus