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P., Couch, Fergus J., Easton, Douglas F., Kraft, Peter ORCID: 0000-0002-4472-8103, Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Garcia-Closas, Montserrat, Schmidt, Marjanka K., Antoniou, Antonis C. and Simard, Jacques (2017). Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genet., 49 (12). S. 1767 - 1779. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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Abstract

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease(1). We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 x 10(-8) with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
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Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Wang, QinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Park, Sue K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomassen, MadsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Droit, ArnaudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bader, Gary D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraft, PeterUNSPECIFIEDorcid.org/0000-0002-4472-8103UNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-210324
DOI: 10.1038/ng.3785
Journal or Publication Title: Nature Genet.
Volume: 49
Number: 12
Page Range: S. 1767 - 1779
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CONFER SUSCEPTIBILITY; FUNCTIONAL VARIANTS; MUTATION CARRIERS; OVARIAN CANCERS; COMMON VARIANTS; MODIFIERS; ENHANCER; REVEALSMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21032

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