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

Nat Genet. 2017 Dec;49(12):1767-1778. doi: 10.1038/ng.3785. Epub 2017 Oct 23.

Abstract

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. 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.

MeSH terms

  • BRCA1 Protein / genetics*
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Heterozygote
  • Humans
  • Mutation*
  • Polymorphism, Single Nucleotide*
  • Receptors, Estrogen / metabolism
  • Risk Factors

Substances

  • BRCA1 Protein
  • Receptors, Estrogen

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