A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer |
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| Authors: | Hunter David J Kraft Peter Jacobs Kevin B Cox David G Yeager Meredith Hankinson Susan E Wacholder Sholom Wang Zhaoming Welch Robert Hutchinson Amy Wang Junwen Yu Kai Chatterjee Nilanjan Orr Nick Willett Walter C Colditz Graham A Ziegler Regina G Berg Christine D Buys Saundra S McCarty Catherine A Feigelson Heather Spencer Calle Eugenia E Thun Michael J Hayes Richard B Tucker Margaret Gerhard Daniela S Fraumeni Joseph F Hoover Robert N Thomas Gilles Chanock Stephen J |
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| Institution: | Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. dhunter@hsph.harvard.edu |
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| 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. |
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