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

2013; Nature Portfolio; Volume: 45; Issue: 12 Linguagem: Inglês

10.1038/ng.2796

1546-1718

David Levine, Weronica E. Ek, Rui Zhang, Xinxue Liu, Lynn Onstad, Cassandra L. Sather, Pierre Lao‐Sirieix, Marilie D. Gammon, Douglas A. Corley, Nicholas J. Shaheen, Nigel C. Bird, Laura J. Hardie, Liam 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.P. Pharoah, Rebecca C. Fitzgerald, Stuart MacGregor, David C. Whiteman, Thomas L. Vaughan,

Helicobacter pylori-related gastroenterology studies

Thomas Vaughan and colleagues report a genome-wide association study of esophageal adenocarcinoma together with its precancerous lesion, Barrett's esophagus. They identified three loci associated with susceptibility to this cancer. 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.