A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma.
We conducted a genome-wide association study of gastric cancer and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 SNPs. We report a combined analysis of 2,240 gastric cancer cases, 2,115 ESCC cases and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex and study, multiple variants at 10q23 had genome-wide significance for gastric cancer and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for gastric cancer (P = 8.40 x 10(-9); per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 x 10(-9); OR = 1.34). The association with gastric cancer differed by anatomic subsite. For tumors in the cardia the association was stronger (P = 4.19 x 10(-15); OR = 1.57), and for those in the noncardia stomach it was absent (P = 0.44; OR = 1.05). Our findings at 10q23 could provide insight into the high incidence of both cancers in China.
Abnet
Christian C
CC
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. abnetc@mail.nih.gov
Freedman
Neal D
ND
Hu
Nan
N
Wang
Zhaoming
Z
Yu
Kai
K
Shu
Xiao-Ou
XO
Yuan
Jian-Min
JM
Zheng
Wei
W
Dawsey
Sanford M
SM
Dong
Linda M
LM
Lee
Maxwell P
MP
Ding
Ti
T
Qiao
You-Lin
YL
Gao
Yu-Tang
YT
Koh
Woon-Puay
WP
Xiang
Yong-Bing
YB
Tang
Ze-Zhong
ZZ
Fan
Jin-Hu
JH
Wang
Chaoyu
C
Wheeler
William
W
Gail
Mitchell H
MH
Yeager
Meredith
M
Yuenger
Jeff
J
Hutchinson
Amy
A
Jacobs
Kevin B
KB
Giffen
Carol A
CA
Burdett
Laurie
L
Fraumeni
Joseph F
JF
Tucker
Margaret A
MA
Chow
Wong-Ho
WH
Goldstein
Alisa M
AM
Chanock
Stephen J
SJ
Taylor
Philip R
PR
D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics*
D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon