DM Levine, WE Ek, R Zhang, X Liu, L Onstad, C Sather, P Lao-Sirieix, MD Gammon, DA Corley, NJ Shaheen, NC Bird, LJ Hardie, LJ Murray, BJ Reid, W-H Chow, HA Risch, O Nyrén, W Ye, G Liu, Y Romero, L Bernstein, AH Wu, AG Casson, SJ Chanock, P Harrington, I Caldas, I Debiram-Beecham, C Caldas, NK Hayward, PD Pharoah, RC Fitzgerald, S Macgregor, DC Whiteman, TL Vaughan
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.