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- Title
A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
- Authors
Levine, David M; Ek, Weronica E; Zhang, Rui; Liu, Xinxue; Onstad, Lynn; Sather, Cassandra; Lao-Sirieix, Pierre; Gammon, Marilie D; Corley, Douglas A; Shaheen, Nicholas J; Bird, Nigel C; Hardie, Laura J; Murray, Liam J; Reid, Brian J; Chow, Wong-Ho; Risch, Harvey A; Nyrén, Olof; Ye, Weimin; Liu, Geoffrey; Romero, Yvonne
- 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.
- Subjects
DISEASE susceptibility; LOCUS (Genetics); ADENOCARCINOMA; BARRETT'S esophagus; DISEASE incidence; GENETIC regulation
- Publication
Nature Genetics, 2013, Vol 45, Issue 12, p1487
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2796