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GWAS Study

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

Levine DM, Ek WE, Zhang R et al.

24121790 PubMed ID
GWAS Study Type
13227 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

LD
Levine DM
EW
Ek WE
ZR
Zhang R
LX
Liu X
OL
Onstad L
SC
Sather C
LP
Lao-Sirieix P
GM
Gammon MD
CD
Corley DA
SN
Shaheen NJ
BN
Bird NC
HL
Hardie LJ
ML
Murray LJ
RB
Reid BJ
CW
Chow WH
RH
Risch HA
NO
Nyrén O
YW
Ye W
LG
Liu G
RY
Romero Y
BL
Bernstein L
WA
Wu AH
CA
Casson AG
CS
Chanock SJ
HP
Harrington P
CI
Caldas I
DI
Debiram-Beecham I
CC
Caldas C
HN
Hayward NK
PP
Pharoah PD
FR
Fitzgerald RC
MS
Macgregor S
WD
Whiteman DC
VT
Vaughan TL
Chapter II

Abstract

Summary of the research findings

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.

1,516 European ancestry cases, 3,209 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

13227
Total Participants
GWAS
Study Type
Yes
Replicated
874 European ancestry cases, 6,911 European ancestry controls
Replication Participants
European
Ancestry
U.K., Sweden, U.S., Australia, Canada, Republic of Ireland
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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Analysis In Progress

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