title: The AIB1 gene polyglutamine repeat length polymorphism and the risk of breast cancer development.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53 Prague 2, Czech Republic. zdekleje@lf1.cuni.cz
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kleibl
authors.forename: Ondrej
authors.initials: O
authors.lastname: Havranek
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kormunda
authors.forename: Jan
authors.initials: J
authors.lastname: Novotny
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Eva
authors.initials: E
authors.lastname: Machackova
authors.forename: Jana
authors.initials: J
authors.lastname: Soukupova
authors.forename: Marketa
authors.initials: M
authors.lastname: Janatova
authors.forename: Spiros
authors.initials: S
authors.lastname: Tavandzis
authors.forename: Petr
authors.initials: P
authors.lastname: Pohlreich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D018153:Czech Republic; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D010455:Peptides; C097188:polyglutamine; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3