A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.
We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.
Petersen
Gloria M
GM
Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Amundadottir
Laufey
L
Fuchs
Charles S
CS
Kraft
Peter
P
Stolzenberg-Solomon
Rachael Z
RZ
Jacobs
Kevin B
KB
Arslan
Alan A
AA
Bueno-de-Mesquita
H Bas
HB
Gallinger
Steven
S
Gross
Myron
M
Helzlsouer
Kathy
K
Holly
Elizabeth A
EA
Jacobs
Eric J
EJ
Klein
Alison P
AP
LaCroix
Andrea
A
Li
Donghui
D
Mandelson
Margaret T
MT
Olson
Sara H
SH
Risch
Harvey A
HA
Zheng
Wei
W
Albanes
Demetrius
D
Bamlet
William R
WR
Berg
Christine D
CD
Boutron-Ruault
Marie-Christine
MC
Buring
Julie E
JE
Bracci
Paige M
PM
Canzian
Federico
F
Clipp
Sandra
S
Cotterchio
Michelle
M
de Andrade
Mariza
M
Duell
Eric J
EJ
Gaziano
J Michael
JM
Giovannucci
Edward L
EL
Goggins
Michael
M
Hallmans
Göran
G
Hankinson
Susan E
SE
Hassan
Manal
M
Howard
Barbara
B
Hunter
David J
DJ
Hutchinson
Amy
A
Jenab
Mazda
M
Kaaks
Rudolf
R
Kooperberg
Charles
C
Krogh
Vittorio
V
Kurtz
Robert C
RC
Lynch
Shannon M
SM
McWilliams
Robert R
RR
Mendelsohn
Julie B
JB
Michaud
Dominique S
DS
Parikh
Hemang
H
Patel
Alpa V
AV
Peeters
Petra H M
PH
Rajkovic
Aleksandar
A
Riboli
Elio
E
Rodriguez
Laudina
L
Seminara
Daniela
D
Shu
Xiao-Ou
XO
Thomas
Gilles
G
Tjønneland
Anne
A
Tobias
Geoffrey S
GS
Trichopoulos
Dimitrios
D
Van Den Eeden
Stephen K
SK
Virtamo
Jarmo
J
Wactawski-Wende
Jean
J
Wang
Zhaoming
Z
Wolpin
Brian M
BM
Yu
Herbert
H
Yu
Kai
K
Zeleniuch-Jacquotte
Anne
A
Fraumeni
Joseph F
JF
Hoover
Robert N
RN
Hartge
Patricia
P
Chanock
Stephen J
SJ
D002277:Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002895:Chromosomes, Human, Pair 5; D015331:Cohort Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide