title: A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer.
abstract: 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.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. dhunter@hsph.harvard.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jacobs
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Nick
authors.initials: N
authors.lastname: Orr
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Graham A
authors.initials: GA
authors.lastname: Colditz
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Saundra S
authors.initials: SS
authors.lastname: Buys
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.forename: Heather Spencer
authors.initials: HS
authors.lastname: Feigelson
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Margaret
authors.initials: M
authors.lastname: Tucker
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Gerhard
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
mesh_terms: 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
chemical_list: C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2