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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
Issue number12
Early online date23 Oct 2017
DateAccepted/In press - 11 Jan 2017
DateE-pub ahead of print - 23 Oct 2017
DatePublished (current) - 1 Dec 2017


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 Please refer to any applicable terms of use of the publisher.

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