A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer.
We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.
Hunter
David J
DJ
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. dhunter@hsph.harvard.edu
Kraft
Peter
P
Jacobs
Kevin B
KB
Cox
David G
DG
Yeager
Meredith
M
Hankinson
Susan E
SE
Wacholder
Sholom
S
Wang
Zhaoming
Z
Welch
Robert
R
Hutchinson
Amy
A
Wang
Junwen
J
Yu
Kai
K
Chatterjee
Nilanjan
N
Orr
Nick
N
Willett
Walter C
WC
Colditz
Graham A
GA
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
Hayes
Richard B
RB
Tucker
Margaret
M
Gerhard
Daniela S
DS
Fraumeni
Joseph F
JF
Hoover
Robert N
RN
Thomas
Gilles
G
Chanock
Stephen J
SJ
D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012307:Risk Factors
C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2