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

  • Jessica Becker
  • Andrea May
  • Christian Gerges
  • Mario Anders
  • Lothar Veits
  • Katharina Weise
  • Darina Czamara
  • Orestis Lyros
  • Hendrik Manner
  • Grischa Terheggen
  • Marino Venerito
  • Tania Noder
  • Rupert Mayershofer
  • Jan-Hinnerk Hofer
  • Hans-Werner Karch
  • Constantin J Ahlbrand
  • Michael Arras
  • Sebastian Hofer
  • Elisabeth Mangold
  • Stefanie Heilmann-Heimbach
  • Sophie K M Heinrichs
  • Timo Hess
  • Ralf Kiesslich
  • Jakob R Izbicki
  • Arnulf H Hölscher
  • Elfriede Bollschweiler
  • Peter Malfertheiner
  • Hauke Lang
  • Markus Moehler
  • Dietmar Lorenz
  • Bertram Müller-Myhsok
  • Katja Ott
  • Thomas Schmidt
  • David C Whiteman
  • Thomas L Vaughan
  • Markus M Nöthen
  • Andreas Hackelsberger
  • Brigitte Schumacher
  • Oliver Pech
  • Yogesh Vashist
  • Michael Vieth
  • Josef Weismüller
  • Horst Neuhaus
  • Thomas Rösch
  • Christian Ell
  • Ines Gockel
  • Johannes Schumacher

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.

Bibliografische Daten

OriginalspracheEnglisch
ISSN0008-5472
DOIs
StatusVeröffentlicht - 11.2015
PubMed 26383589