Identification of Four Novel Susceptibility Loci for Oestrogen Receptor Negative Breast Cancer

Nat Commun. 2016 Apr 27;7:11375. doi: 10.1038/ncomms11375.

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • Breast Neoplasms / genetics*
  • Chromosomes, Human, Pair 2 / genetics
  • Cyclophilins / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods*
  • Genotype
  • Heterozygote
  • Humans
  • Mutation
  • Polymorphism, Single Nucleotide
  • Receptors, Estrogen / genetics*
  • Risk Factors
  • tRNA Methyltransferases

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Receptors, Estrogen
  • Trmt61B protein, human
  • tRNA Methyltransferases
  • Cyclophilins
  • cyclophilin J, human