ABCTB Investigators, EMBRACE, GEMO Study Collaborators et al. (3 more authors) (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics, 49 (12). pp. 1767-1778. ISSN 1061-4036
Abstract
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. 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 × 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Nature America, 2017. This is an author produced version of a paper subsequently published in Nature Genetics. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number CANCER RESEARCH UK (CRUK) C5410/A7315. BREAST CANCER NOW UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Jan 2017 11:31 |
Last Modified: | 23 Apr 2018 00:38 |
Published Version: | https://doi.org/10.1038/ng.3785 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/ng.3785 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110627 |