Association of ESR1 gene tagging SNPs with breast cancer risk.
We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c-allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t-allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.
Dunning
Alison M
AM
Department of Oncology, University of Cambridge, Cambridge, UK. alisond@srl.cam.ac.uk
Healey
Catherine S
CS
Baynes
Caroline
C
Maia
Ana-Teresa
AT
Scollen
Serena
S
Vega
Ana
A
Rodríguez
Raquel
R
Barbosa-Morais
Nuno L
NL
Ponder
Bruce A J
BA
Low
Yen-Ling
YL
Bingham
Sheila
S
Haiman
Christopher A
CA
Le Marchand
Loic
L
Broeks
Annegien
A
Schmidt
Marjanka K
MK
Hopper
John
J
Southey
Melissa
M
Beckmann
Matthias W
MW
Fasching
Peter A
PA
Peto
Julian
J
Johnson
Nichola
N
Bojesen
Stig E
SE
Nordestgaard
Børge
B
Milne
Roger L
RL
Benitez
Javier
J
Hamann
Ute
U
Ko
Yon
Y
Schmutzler
Rita K
RK
Burwinkel
Barbara
B
Schürmann
Peter
P
Dörk
Thilo
T
Heikkinen
Tuomas
T
Nevanlinna
Heli
H
Lindblom
Annika
A
Margolin
Sara
S
Mannermaa
Arto
A
Kosma
Veli-Matti
VM
Chen
Xiaoqing
X
Spurdle
Amanda
A
Change-Claude
Jenny
J
Flesch-Janys
Dieter
D
Couch
Fergus J
FJ
Olson
Janet E
JE
Severi
Gianluca
G
Baglietto
Laura
L
Børresen-Dale
Anne-Lise
AL
Kristensen
Vessela
V
Hunter
David J
DJ
Hankinson
Susan E
SE
Devilee
Peter
P
Vreeswijk
Maaike
M
Lissowska
Jolanta
J
Brinton
Louise
L
Liu
Jianjun
J
Hall
Per
P
Kang
Daehee
D
Yoo
Keun-Young
KY
Shen
Chen-Yang
CY
Yu
Jyh-Cherng
JC
Anton-Culver
Hoda
H
Ziogoas
Argyrios
A
Sigurdson
Alice
A
Struewing
Jeff
J
Easton
Douglas F
DF
Garcia-Closas
Montserrat
M
Humphreys
Manjeet K
MK
Morrison
Jonathan
J
Pharoah
Paul D P
PD
Pooley
Karen A
KA
Chenevix-Trench
Georgia
G
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012334:RNA, Neoplasm