Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

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  • Fergus J Couch
  • Karoline B Kuchenbaecker
  • Kyriaki Michailidou
  • Gustavo A Mendoza-Fandino
  • Silje Nord
  • Janna Lilyquist
  • Curtis Olswold
  • Emily Hallberg
  • Simona Agata
  • Habibul Ahsan
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  • Raymonda Varon-Mateeva
  • Zhaoming Wang
  • Shan Wang-Gohrke
  • Elisabete Weiderpass
  • Jeffrey N Weitzel
  • Alice S Whittemore
  • Hans Wildiers
  • Robert Winqvist
  • Xiaohong R Yang
  • Drakoulis Yannoukakos
  • Song Yao
  • M Pilar Zamora
  • Wei Zheng
  • Per Hall
  • Peter Kraft
  • Celine Vachon
  • Susan Slager
  • Georgia Chenevix-Trench
  • Paul P D Pharoah
  • Alvaro N A Monteiro
  • Montserrat García-Closas
  • Douglas F Easton
  • Antonis C Antoniou

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.

Original languageEnglish
Article number11375
JournalNature Communications
Volume7
Pages (from-to)1-13
Number of pages13
ISSN2041-1723
DOIs
Publication statusPublished - 2016

    Research areas

  • Journal Article

ID: 177067393