PURPOSE: 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. METHODS: 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. RESULTS: Having used previously published statistical analyses of AIB1 poly-Q repeat length (≥28 and ≥29 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). CONCLUSIONS: 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.
PURPOSE: 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. METHODS: We genotyped AIB1poly-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 AIB1poly-Q repeat length polymorphism on BC onset. RESULTS: Having used previously published statistical analyses of AIB1poly-Q repeat length (≥28 and ≥29 repeat cutpoints or analysis of AIB1poly-Q repeat length as continuous variable), we did not find any association between AIB1poly-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). CONCLUSIONS: Our results confirm that AIB1poly-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.
Authors: D Ford; D F Easton; M Stratton; S Narod; D Goldgar; P Devilee; D T Bishop; B Weber; G Lenoir; J Chang-Claude; H Sobol; M D Teare; J Struewing; A Arason; S Scherneck; J Peto; T R Rebbeck; P Tonin; S Neuhausen; R Barkardottir; J Eyfjord; H Lynch; B A Ponder; S A Gayther; M Zelada-Hedman Journal: Am J Hum Genet Date: 1998-03 Impact factor: 11.025
Authors: Tyler Lahusen; Ralf T Henke; Benjamin L Kagan; Anton Wellstein; Anna T Riegel Journal: Breast Cancer Res Treat Date: 2009-05-06 Impact factor: 4.872
Authors: Luna Kadouri; Zsofia Kote-Jarai; Douglas F Easton; Ayala Hubert; Rifat Hamoudi; Benjamin Glaser; Dvorah Abeliovich; Tamar Peretz; Rosalind A Eeles Journal: Int J Cancer Date: 2004-01-20 Impact factor: 7.396
Authors: Petr Pohlreich; Michal Zikan; Jana Stribrna; Zdenek Kleibl; Marketa Janatova; Jaroslav Kotlas; Jana Zidovska; Jan Novotny; Lubos Petruzelka; Csilla Szabo; Bohuslav Matous Journal: Breast Cancer Res Date: 2005-07-19 Impact factor: 6.466
Authors: Karen G Montgomery; Jiun-Horng Chang; Dorota M Gertig; Gillian S Dite; Margaret R McCredie; Graham G Giles; Melissa C Southey; John L Hopper; Ian G Campbell Journal: Breast Cancer Res Date: 2005-03-04 Impact factor: 6.466
Authors: Aida Bianco; Barbara Quaresima; Claudia Pileggi; Maria Concetta Faniello; Carlo De Lorenzo; Francesco Costanzo; Maria Pavia Journal: PLoS One Date: 2013-03-06 Impact factor: 3.240