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

Abstract

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.

Fig. 1

Effect of AIB1 genotype consisting of 28/28 glutamine repeats on development of BC in patients carrying mutations in BRCA1 and BRCA2 genes. a Entire group of BRCA1 mutation carriers (P values using Log-rank and Wilcoxon test were 0.04 and 0.2, respectively). b Carriers of BRCA1 mutation localized in exon 2–11 (P values using Log-rank and Wilcoxon test were 0.06 and 0.2, respectively). c Entire group of BRCA2 mutation carriers (P values using Log-rank and Wilcoxon test were 0.2 and 0.3, respectively). d Carriers of BRCA2 mutation localized in exon 11 (P values using Log-rank and Wilcoxon test were 0.009 and 0.01, respectively). Note: Cox model hazard ratios (HR) and 95% HR confidence intervals (CI) for analyzed groups are indicated in the graphs