title: A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
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.
authors.affiliation: Department of Biostatistics, University of Washington, School of Public Health, Seattle, Washington, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Levine
authors.forename: Weronica E
authors.initials: WE
authors.lastname: Ek
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liu
authors.forename: Lynn
authors.initials: L
authors.lastname: Onstad
authors.forename: Cassandra
authors.initials: C
authors.lastname: Sather
authors.forename: Pierre
authors.initials: P
authors.lastname: Lao-Sirieix
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Corley
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Bird
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Hardie
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murray
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.forename: Olof
authors.initials: O
authors.lastname: Nyrén
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Romero
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.forename: Alan G
authors.initials: AG
authors.lastname: Casson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Patricia
authors.initials: P
authors.lastname: Harrington
authors.forename: Isabel
authors.initials: I
authors.lastname: Caldas
authors.forename: Irene
authors.initials: I
authors.lastname: Debiram-Beecham
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Paul D
authors.identifier: 000000018494732X
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fitzgerald
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D001471:Barrett Esophagus / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide