Association of NCOA3 polymorphisms with breast cancer risk.
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.
Burwinkel
Barbara
B
Division of Molecular Genetic Epidemiology C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. b.burwinkel@dkfz.de
Wirtenberger
Michael
M
Klaes
Rüdiger
R
Schmutzler
Rita K
RK
Grzybowska
Ewa
E
Försti
Asta
A
Frank
Bernd
B
Bermejo
Justo Lorenzo
JL
Bugert
Peter
P
Wappenschmidt
Barbara
B
Butkiewicz
Dorota
D
Pamula
Jolanta
J
Pekala
Wioletta
W
Zientek
Helena
H
Mielzynska
Danuta
D
Siwinska
Ewa
E
Bartram
Claus R
CR
Hemminki
Kari
K
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*
D015513:Oncogene Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3