A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus

David M. Levine, Weronica E. Ek, Rui Zhang, Xinxue Liu, Lynn Onstad, Cassandra Sather, Pierre Lao-Sirieix, Marilie D. Gammon, Douglas A. Corley, Nicholas J. Shaheen, Nigel C. Bird, Laura J. Hardie, Liam J. Murray, Brian J. Reid, Wong-Ho Chow, Harvey A. Risch, Olof Nyrén, Weimin Ye, Geoffrey Liu, Yvonne RomeroLeslie Bernstein, Anna H. Wu, Alan G. Casson, Stephen J. Chanock, Patricia Harrington, Isabel Caldas, Irene Debiram-Beecham, Carlos Caldas, Nicholas K. Hayward, Paul D. Pharoah, Rebecca C. Fitzgerald, Stuart MacGregor, David C. Whiteman, Thomas L. Vaughan

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133 Citations (Scopus)

Abstract

Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10(-10)) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10(-9)) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10(-9)) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma.
Original languageEnglish
Pages (from-to)1487–1493
Number of pages9
JournalNature Genetics
Volume45
Issue number12
DOIs
Publication statusPublished - Dec 2013

ASJC Scopus subject areas

  • Genetics

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