title: Association of NCOA3 polymorphisms with breast cancer risk.
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.
authors.affiliation: Division of Molecular Genetic Epidemiology C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. b.burwinkel@dkfz.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Michael
authors.initials: M
authors.lastname: Wirtenberger
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klaes
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Ewa
authors.initials: E
authors.lastname: Grzybowska
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.forename: Bernd
authors.initials: B
authors.lastname: Frank
authors.forename: Justo Lorenzo
authors.initials: JL
authors.lastname: Bermejo
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Jolanta
authors.initials: J
authors.lastname: Pamula
authors.forename: Wioletta
authors.initials: W
authors.lastname: Pekala
authors.forename: Helena
authors.initials: H
authors.lastname: Zientek
authors.forename: Danuta
authors.initials: D
authors.lastname: Mielzynska
authors.forename: Ewa
authors.initials: E
authors.lastname: Siwinska
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D000123:Acetyltransferases; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D051548:Histone Acetyltransferases; D006801:Humans; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D011044:Poland; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D015513:Oncogene Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3