A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease.
Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.
Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Worts Causeway, Cambridge CB1 8RN, UK.
Ali
A
Amin Al Olama
Zsofia
Z
Kote-Jarai
Fredrick R
FR
Schumacher
Fredrik
F
Wiklund
Sonja I
SI
Berndt
Sara
S
Benlloch
Graham G
GG
Giles
Gianluca
G
Severi
David E
DE
Neal
Freddie C
FC
Hamdy
Jenny L
JL
Donovan
David J
DJ
Hunter
Brian E
BE
Henderson
Michael J
MJ
Thun
Michael
M
Gaziano
Edward L
EL
Giovannucci
Afshan
A
Siddiq
Ruth C
RC
Travis
David G
DG
Cox
Federico
F
Canzian
Elio
E
Riboli
Timothy J
TJ
Key
Gerald
G
Andriole
Demetrius
D
Albanes
Richard B
RB
Hayes
Johanna
J
Schleutker
Anssi
A
Auvinen
Teuvo L J
TL
Tammela
Maren
M
Weischer
Janet L
JL
Stanford
Elaine A
EA
Ostrander
Cezary
C
Cybulski
Jan
J
Lubinski
Stephen N
SN
Thibodeau
Daniel J
DJ
Schaid
Karina D
KD
Sorensen
Jyotsna
J
Batra
Judith A
JA
Clements
Suzanne
S
Chambers
Joanne
J
Aitken
Robert A
RA
Gardiner
Christiane
C
Maier
Walther
W
Vogel
Thilo
T
Dörk
Hermann
H
Brenner
Tomonori
T
Habuchi
Sue
S
Ingles
Esther M
EM
John
Joanne L
JL
Dickinson
Lisa
L
Cannon-Albright
Manuel R
MR
Teixeira
Radka
R
Kaneva
Hong-Wei
HW
Zhang
Yong-Jie
YJ
Lu
Jong Y
JY
Park
Kathleen A
KA
Cooney
Kenneth R
KR
Muir
Daniel A
DA
Leongamornlert
Edward
E
Saunders
Malgorzata
M
Tymrakiewicz
Nadiya
N
Mahmud
Michelle
M
Guy
Koveela
K
Govindasami
Lynne T
LT
O'Brien
Rosemary A
RA
Wilkinson
Amanda L
AL
Hall
Emma J
EJ
Sawyer
Tokhir
T
Dadaev
Jonathan
J
Morrison
David P
DP
Dearnaley
Alan
A
Horwich
Robert A
RA
Huddart
Vincent S
VS
Khoo
Christopher C
CC
Parker
Nicholas
N
Van As
Christopher J
CJ
Woodhouse
Alan
A
Thompson
Tim
T
Dudderidge
Chris
C
Ogden
Colin S
CS
Cooper
Artitaya
A
Lophatonanon
Melissa C
MC
Southey
John L
JL
Hopper
Dallas
D
English
Jarmo
J
Virtamo
Loic
L
Le Marchand
Daniele
D
Campa
Rudolf
R
Kaaks
Sara
S
Lindstrom
W Ryan
WR
Diver
Susan
S
Gapstur
Meredith
M
Yeager
Angela
A
Cox
Mariana C
MC
Stern
Roman
R
Corral
Markus
M
Aly
William
W
Isaacs
Jan
J
Adolfsson
Jianfeng
J
Xu
S Lilly
SL
Zheng
Tiina
T
Wahlfors
Kimmo
K
Taari
Paula
P
Kujala
Peter
P
Klarskov
Børge G
BG
Nordestgaard
M Andreas
MA
Røder
Ruth
R
Frikke-Schmidt
Stig E
SE
Bojesen
Liesel M
LM
FitzGerald
Suzanne
S
Kolb
Erika M
EM
Kwon
Danielle M
DM
Karyadi
Torben Falck
TF
Orntoft
Michael
M
Borre
Antje
A
Rinckleb
Manuel
M
Luedeke
Kathleen
K
Herkommer
Andreas
A
Meyer
Jürgen
J
Serth
James R
JR
Marthick
Briony
B
Patterson
Dominika
D
Wokolorczyk
Amanda
A
Spurdle
Felicity
F
Lose
Shannon K
SK
McDonnell
Amit D
AD
Joshi
Ahva
A
Shahabi
Pedro
P
Pinto
Joana
J
Santos
Ana
A
Ray
Thomas A
TA
Sellers
Hui-Yi
HY
Lin
Robert A
RA
Stephenson
Craig
C
Teerlink
Heiko
H
Muller
Dietrich
D
Rothenbacher
Norihiko
N
Tsuchiya
Shintaro
S
Narita
Guang-Wen
GW
Cao
Chavdar
C
Slavov
Vanio
V
Mitev
Stephen
S
Chanock
Henrik
H
Gronberg
Christopher A
CA
Haiman
Peter
P
Kraft
Douglas F
DF
Easton
Rosalind A
RA
Eeles
D016022:Case-Control Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D040641:Quantitative Trait Loci; D015203:Reproducibility of Results