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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Roger L Milne
  • Karoline B Kuchenbaecker
  • Kyriaki Michailidou
  • Jonathan Beesley
  • Siddhartha Kar
  • Sara Lindström
  • Shirley Hui
  • Audrey Lemaçon
  • Penny Soucy
  • Joe Dennis
  • Xia Jiang
  • Asha Rostamianfar
  • Hilary Finucane
  • Manjeet K Bolla
  • Lesley McGuffog
  • Qin Wang
  • Cora M Aalfs
  • ABCTB Investigators
  • Marcia Adams
  • Julian Adlard
  • Simona Agata
  • Shahana Ahmed
  • Habibul Ahsan
  • Kristiina Aittomäki
  • Fares Al-Ejeh
  • Jamie Allen
  • Christine B Ambrosone
  • Christopher I Amos
  • Irene L Andrulis
  • Hoda Anton-Culver
  • Natalia N Antonenkova
  • Volker Arndt
  • Norbert Arnold
  • Kristan J Aronson
  • Bernd Auber
  • Paul L Auer
  • Margreet G E M Ausems
  • Jacopo Azzollini
  • François Bacot
  • Judith Balmaña
  • Bojesen, Stig Egil
  • Gerdes, Anne-Marie Axø
  • Lænkholm, Anne-Vibeke
  • Nordestgaard, Børge
  • Marjanka K Schmidt
  • Antonis C Antoniou
  • Jacques Simard

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.

Original languageEnglish
JournalNature Genetics
Issue number12
Pages (from-to)1767-1778
Publication statusPublished - 2017

    Research areas

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

ID: 195042726