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Cancer Med. 2015 Nov;4(11):1700-4. doi: 10.1002/cam4.500. Epub 2015 Aug 15.

Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma.

Author information

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
Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Kinikum, Berlin, Germany.
7
Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
8
Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
9
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
10
Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany.
11
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.
12
Gastroenterologie am Burgweiher, Bonn, Germany.
13
Magen Darm Zentrum Wiener Platz, Cologne, Germany.
14
Gastroenterologische Schwerpunktpraxis, Baumholder, Germany.
15
Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
16
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
17
Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
18
First Department of Internal Medicine, University Medical Center, University of Mainz, Mainz, Germany.
19
Department of General and Visceral Surgery, Sana Klinikum, Offenbach, Germany.
20
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
21
Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany.
22
Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
23
Department of Epidemiology, University of Washington, School of Public Health, Seattle, Washington.
24
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
25
Gastropraxis, Wiesbaden, Germany.
26
Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
27
Department of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany.
28
Gastroenterologische Gemeinschaftspraxis, Koblenz, Germany.

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.

KEYWORDS:

BARX1; FOXF1; FOXP1; esophageal adenocarcinoma; genetic association study

PMID:
26383589
PMCID:
PMC4673997
DOI:
10.1002/cam4.500
[Indexed for MEDLINE]
Free PMC Article

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