The AIB1 gene polyglutamine repeat length polymorphism and the risk of breast cancer development

Autoři	KLEIBL Zdenek HAVRÁNEK Ondrej KORMUNDA Stanislav NOVOTNY Jan FORETOVÁ Lenka MACHACKOVA Eva SOUKUPOVA Jana JANATOVA Markéta TAVANDZIS Spiros POHLREICH Petr
Rok publikování	2011
Druh	Článek v odborném periodiku
Časopis / Zdroj	Journal of cancer research and clinical oncology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1007/s00432-010-0889-5
Obor	Ostatní lékařské obory
Klíčová slova	Amplified in breast cancer 1 (AIB1/SRC-3/NCoA3) gene; Polymorphism; CAA/CAG repeat; Breast cancer; BRCA1; BRCA2
Popis	Carriers of BRCA1/2 mutations are at high lifetime risk of breast cancer (BC); however, the BC onset broadly vary in individual patients. Recently, polyglutamine (poly-Q) repeat length polymorphism of the amplified in breast cancer 1 (AIB1) gene was analyzed as a risk factor influencing BC onset in BRCA1/2 mutation carriers with contradictory results. We genotyped AIB1 poly-Q repeat in 243 BRCA1/2 mutation carriers, 61 patients with familial BC (negatively tested for the presence of BRCA1/2 mutation), 221 patients with sporadic BC, and 176 non-cancer controls using denaturing high-performance liquid chromatography and statistically evaluated the effect of AIB1 poly-Q repeat length polymorphism on BC onset. Having used previously published statistical analyses of AIB1 poly-Q repeat length (a parts per thousand yen28 and a parts per thousand yen29 repeat cutpoints or analysis of AIB1 poly-Q repeat length as continuous variable), we did not find any association between AIB1 poly-Q repeat length and BC development in analyzed BC groups. However, the analysis of individual genotypes revealed that AIB1 genotype consisting of 28/28 glutamine repeats served as a protective factor in BRCA1 mutation carriers (HR = 0.64; 95% CI 0.41-0.99; P = 0.045) and as a risk factor in carriers of mutation in exon 11 of the BRCA2 gene (HR = 3.50; 95% CI 1.25-9.78; P = 0.017). Our results confirm that AIB1 poly-Q repeat length polymorphism does not influence the BC risk in general but suggest that the specific AIB1 genotypes should be considered in patients with BC carrying mutation in the BRCA1/2 genes.