Polyglutamine repeat length in the NCOA3 does not affect risk in familial breast cancer.

The nuclear receptor coactivator 3 (NCOA3) is a protein that binds to nuclear hormone receptors and thereby facilitates the expression of downstream genes. The NCOA3 gene has been found to be overexpressed in breast tumors (1). On exon 21, the NCOA3 gene contains a polymorphic region with a trinucleotide repeat encoding a polyglutamine repeat in the COOH terminus of the NCOA3 protein. Longer repeat lengths have been shown to correlate with higher breast cancer risk in BRCA1 and BRCA2 (BRCA1/2) mutation carriers, whereas shorter alleles seem to have a protective effect (2, 3). However, the NCOA3 polyglutamine repeat length alone has not been found to alter the breast cancer risk among unselected postmenopausal women (4). Unlike these studies, we used for the first time a large set of DNA samples from women with familial breast cancer, where the likelihood to detect possible risk factors is much higher than in unselected cases. To prove if the NCOA3 polymorphism has an impact on the breast cancer risk, we analyzed 591 breast cancer samples from German and Polish women together with 536 matched controls.