A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer

Hunter, David J and Kraft, Peter and Jacobs, Kevin B and Cox, David G and Yeager, Meredith and Hankinson, Susan E and Wacholder, Sholom and Wang, Zhaoming and Welch, Robert and Hutchinson, Amy and Wang, Junwen and Yu, Kai and Chatterjee, Nilanjan and Orr, Nick and Willett, Walter C and Colditz, Graham A and Ziegler, Regina G and Berg, Christine D and Buys, Saundra S and McCarty, Catherine A and Feigelson, Heather Spencer and Calle, Eugenia E and Thun, Michael J and Hayes, Richard B and Tucker, Margaret and Gerhard, Daniela S and Fraumeni, Joseph F, Jr and Hoover, Robert N and Thomas, Gilles and Chanock, Stephen J (2007) A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nature Genetics, 39. pp. 870-874.

DRUM DOI

https://doi.org/10.13016/yypf-npwm

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 (Ptrend for the most strongly associated SNP (rs1219648) = 1.1 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