Association of NCOA3 polymorphisms with breast cancer risk

Clin Cancer Res. 2005 Mar 15;11(6):2169-74. doi: 10.1158/1078-0432.CCR-04-1621.


The nuclear receptor coactivator 3 (NCOA3, also known as AIB1) is a coactivator of nuclear receptors like the estrogen receptor. NCOA3 is overexpressed in approximately 60% of primary human breast tumors, and high levels of NCOA3 expression are associated with tamoxifen resistance and worse survival rate. In contrast, NCOA3 deficiency suppresses v-Ha-ras-induced breast cancer initiation and progression in mice. Here, we analyzed the influence of NCOA3 coding single nucleotide polymorphisms on breast cancer risk by performing a case-control study using a German and a Polish study population and identified an association between NCOA3 polymorphisms and breast cancer. A joint analysis of the German and the Polish study population revealed a significant protective effect for the 1758G>C (Q586H) and 2880A>G (T960T) variants. In addition, haplotype analysis showed a protective effect of the 1758C-2880A and 1758G-2880G haplotypes (odds ratio 0.79; 95% confidence interval, 0.67-0.93; P = 0.004). Because of the impact of NCOA3 in antiestrogen therapy resistance, these polymorphisms might also influence therapy outcome in breast cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Female
  • Germany
  • Haplotypes / genetics
  • Histone Acetyltransferases
  • Humans
  • Middle Aged
  • Nuclear Receptor Coactivator 3
  • Oncogene Proteins
  • Poland
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Trans-Activators / genetics*


  • Oncogene Proteins
  • Trans-Activators
  • Acetyltransferases
  • Histone Acetyltransferases
  • NCOA3 protein, human
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 3