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Association of NCOA3 (AIB1) polymorphisms with breast cancer risk

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The nuclear receptor coactivator 3 (NCOA3, also known as AIB1) is a coactivator of nuclear receptors like the estrogen receptor. NCOA3 is overexpressed in ~60% of primary human breast tumours, 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 analysed 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 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). Due to the impact of NCOA3 in anti-estrogen therapy resistance, these polymorphisms might also influence therapy outcome in breast cancer.

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BB and MW contributed equally to this work.

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Burwinkel, B., Wirtenberger, M., Frank, B. et al. Association of NCOA3 (AIB1) polymorphisms with breast cancer risk. Breast Cancer Res 7, P1.20 (2005) doi:10.1186/bcr1107

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Keywords

  • Breast Cancer
  • Tamoxifen
  • Breast Cancer Risk
  • Nuclear Receptor
  • Human Breast Tumour