1. Association of NCOA3 polymorphisms with breast cancer risk.
- Author
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Burwinkel B, Wirtenberger M, Klaes R, Schmutzler RK, Grzybowska E, Försti A, Frank B, Bermejo JL, Bugert P, Wappenschmidt B, Butkiewicz D, Pamula J, Pekala W, Zientek H, Mielzynska D, Siwinska E, Bartram CR, and Hemminki K
- Subjects
- Acetyltransferases, Case-Control Studies, Female, Germany, Haplotypes genetics, Histone Acetyltransferases, Humans, Middle Aged, Nuclear Receptor Coactivator 3, Oncogene Proteins, Poland, Risk Factors, Breast Neoplasms genetics, Polymorphism, Single Nucleotide genetics, Trans-Activators genetics
- Abstract
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.
- Published
- 2005
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