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

Overview

MeSH Major

  • Breast Neoplasms
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromosomes, Human, Pair 6
  • Estrogen Receptor alpha

abstract

  • 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.

authors

publication date

  • March 29, 2016

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC4938803

Digital Object Identifier (DOI)

  • 10.1038/ng.3521

PubMed ID

  • 26928228

Additional Document Info

start page

  • 374

end page

  • 86

volume

  • 48

number

  • 4