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

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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

109 Citations (Scopus)
424 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1767-1778
Number of pages12
JournalNature Genetics
Volume49
Issue number12
Early online date23 Oct 2017
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • 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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