Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

Research output: Contribution to journalJournal articleResearchpeer-review

  • Alison M Dunning
  • Kyriaki Michailidou
  • Karoline B Kuchenbaecker
  • Deborah Thompson
  • Juliet D French
  • Jonathan Beesley
  • Catherine S Healey
  • Siddhartha Kar
  • Karen A Pooley
  • Elena Lopez-Knowles
  • Ed Dicks
  • Daniel Barrowdale
  • Nicholas A Sinnott-Armstrong
  • Richard C Sallari
  • Kristine M Hillman
  • Susanne Kaufmann
  • Haran Sivakumaran
  • Mahdi Moradi Marjaneh
  • Jason S Lee
  • Margaret Hills
  • Monika Jarosz
  • Suzie Drury
  • Sander Canisius
  • Manjeet K Bolla
  • Joe Dennis
  • Qin Wang
  • John L Hopper
  • Melissa C Southey
  • Annegien Broeks
  • Marjanka K Schmidt
  • Artitaya Lophatananon
  • Kenneth Muir
  • Matthias W Beckmann
  • Peter A Fasching
  • Isabel Dos-Santos-Silva
  • Julian Peto
  • Elinor J Sawyer
  • Ian Tomlinson
  • Barbara Burwinkel
  • Frederik Marme
  • Pascal Guénel
  • Thérèse Truong
  • Bojesen, Stig Egil
  • Henrik Lavlund Flyger
  • Anna González-Neira
  • Jose I A Perez
  • Hoda Anton-Culver
  • Lee Eunjung
  • Volker Arndt
  • Hermann Brenner

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

Original languageEnglish
JournalNature Genetics
Issue number4
Pages (from-to)374-86
Number of pages13
Publication statusPublished - 2016

    Research areas

  • Base Sequence, Breast Neoplasms, Carrier Proteins, Cell Cycle Proteins, Chromosomes, Human, Pair 6, Estrogen Receptor alpha, Female, Gene Expression, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Phenotype, Polymorphism, Single Nucleotide, Protein Binding, Risk Factors, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.

ID: 171997073