Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2.
Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.
Ahmed
Shahana
S
Department of Oncology, University of Cambridge, UK.
Thomas
Gilles
G
Ghoussaini
Maya
M
Healey
Catherine S
CS
Humphreys
Manjeet K
MK
Platte
Radka
R
Morrison
Jonathan
J
Maranian
Melanie
M
Pooley
Karen A
KA
Luben
Robert
R
Eccles
Diana
D
Evans
D Gareth
DG
Fletcher
Olivia
O
Johnson
Nichola
N
dos Santos Silva
Isabel
I
Peto
Julian
J
Stratton
Michael R
MR
Rahman
Nazneen
N
Jacobs
Kevin
K
Prentice
Ross
R
Anderson
Garnet L
GL
Rajkovic
Aleksandar
A
Curb
J David
JD
Ziegler
Regina G
RG
Berg
Christine D
CD
Buys
Saundra S
SS
McCarty
Catherine A
CA
Feigelson
Heather Spencer
HS
Calle
Eugenia E
EE
Thun
Michael J
MJ
Diver
W Ryan
WR
Bojesen
Stig
S
Nordestgaard
Børge G
BG
Flyger
Henrik
H
Dörk
Thilo
T
Schürmann
Peter
P
Hillemanns
Peter
P
Karstens
Johann H
JH
Bogdanova
Natalia V
NV
Antonenkova
Natalia N
NN
Zalutsky
Iosif V
IV
Bermisheva
Marina
M
Fedorova
Sardana
S
Khusnutdinova
Elza
E
Kang
Daehee
D
Yoo
Keun-Young
KY
Noh
Dong Young
DY
Ahn
Sei-Hyun
SH
Devilee
Peter
P
van Asperen
Christi J
CJ
Tollenaar
R A E M
RA
Seynaeve
Caroline
C
Garcia-Closas
Montserrat
M
Lissowska
Jolanta
J
Brinton
Louise
L
Peplonska
Beata
B
Nevanlinna
Heli
H
Heikkinen
Tuomas
T
Aittomäki
Kristiina
K
Blomqvist
Carl
C
Hopper
John L
JL
Southey
Melissa C
MC
Smith
Letitia
L
Spurdle
Amanda B
AB
Schmidt
Marjanka K
MK
Broeks
Annegien
A
van Hien
Richard R
RR
Cornelissen
Sten
S
Milne
Roger L
RL
Ribas
Gloria
G
González-Neira
Anna
A
Benitez
Javier
J
Schmutzler
Rita K
RK
Burwinkel
Barbara
B
Bartram
Claus R
CR
Meindl
Alfons
A
Brauch
Hiltrud
H
Justenhoven
Christina
C
Hamann
Ute
U
Chang-Claude
Jenny
J
Hein
Rebecca
R
Wang-Gohrke
Shan
S
Lindblom
Annika
A
Margolin
Sara
S
Mannermaa
Arto
A
Kosma
Veli-Matti
VM
Kataja
Vesa
V
Olson
Janet E
JE
Wang
Xianshu
X
Fredericksen
Zachary
Z
Giles
Graham G
GG
Severi
Gianluca
G
Baglietto
Laura
L
English
Dallas R
DR
Hankinson
Susan E
SE
Cox
David G
DG
Kraft
Peter
P
Vatten
Lars J
LJ
Hveem
Kristian
K
Kumle
Merethe
M
Sigurdson
Alice
A
Doody
Michele
M
Bhatti
Parveen
P
Alexander
Bruce H
BH
Hooning
Maartje J
MJ
van den Ouweland
Ans M W
AM
Oldenburg
Rogier A
RA
Schutte
Mieke
M
Hall
Per
P
Czene
Kamila
K
Liu
Jianjun
J
Li
Yuqing
Y
Cox
Angela
A
Elliott
Graeme
G
Brock
Ian
I
Reed
Malcolm W R
MW
Shen
Chen-Yang
CY
Yu
Jyh-Cherng
JC
Hsu
Giu-Cheng
GC
Chen
Shou-Tung
ST
Anton-Culver
Hoda
H
Ziogas
Argyrios
A
Andrulis
Irene L
IL
Knight
Julia A
JA
Beesley
Jonathan
J
Goode
Ellen L
EL
Couch
Fergus
F
Chenevix-Trench
Georgia
G
Hoover
Robert N
RN
Ponder
Bruce A J
BA
Hunter
David J
DJ
Pharoah
Paul D P
PD
Dunning
Alison M
AM
Chanock
Stephen J
SJ
Easton
Douglas F
DF