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

被引：1167

作者：

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., Jr.

Hoover, Robert N.

Thomas, Gilles

Chanock, Stephen J.

机构：

[1] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[4] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA

[5] MIT, Broad Inst, Cambridge, MA 02142 USA

[6] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA

[7] Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA

[8] SAIC Frederick, NCI FCRDC, Frederick, MD 21702 USA

[9] NCI, Pediat Oncol Branch, Canc Res Ctr, NIH,DHHS, Bethesda, MD USA

[10] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[11] Washington Univ, Sch Med, St Louis, MO 63130 USA

[12] NCI, Div Canc Prevent, NIH, DHHS, Bethesda, MD 20892 USA

[13] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA

[14] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI 54449 USA

[15] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA

[16] NCI, Off Canc Genom, NIH, DHHS, Bethesda, MD 20892 USA

来源：

NATURE GENETICS | 2007年 / 39卷 / 07期

关键词：

D O I：

10.1038/ng2075

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：870 / 874

页数：5

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