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Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Research output: Contribution to journalArticle

  • the Breast Cancer Association Consortium (BCAC)
  • the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
  • Roger L. Milne
  • Judith S. Brand
  • Kenneth Muir
  • Antonis C. Antoniou
Original languageEnglish
Pages (from-to)1767-1778
Number of pages12
JournalNature Genetics
Volume49
Issue number12
Early online date23 Oct 2017
DOIs
DateAccepted/In press - 11 Jan 2017
DateE-pub ahead of print - 23 Oct 2017
DatePublished (current) - 1 Dec 2017

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.

    Research areas

  • BRCA1 Protein, Breast Neoplasms, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterozygote, Humans, Mutation, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Factors, Journal Article

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/ng.3785#abstract. Please refer to any applicable terms of use of the publisher.

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