After four years of effort on the part of our team, we published the main results from our GWAS in Nature Genetics, finding four new loci for esophageal adenocarcinoma.

Nature Genetics doi:10.1038/ng.2796

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 Romero, Leslie 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

Link to Nature Genetics

Link to FHCRC press release


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.


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Clockwise from top: Dave Levine, Weronica Ek, Rui Zhang, Rebecca Fitzgerald, Stuart MacGregor, David Whiteman and Thomas Vaughan