The AIB1 gene polyglutamine repeat length polymorphism contributes to risk of epithelial ovarian cancer risk: a case-control study.

Genes coding for proteins involved in steroid hormone signaling have been identified as ovarian cancer risk-modifier candidates. AIB1 gene (amplified in breast cancer-1), an androgen receptor (AR) coactivator, expresses a polyglutamine (poly-Q) sequence within the carboxyl-terminal coding region. We hypothesized that genotypic variations in the androgen-signaling pathway promote aggressive epithelial ovarian cancer biology and sought to examine the effect of AIB1 poly-Q repeat length on ovarian cancer risk with a case-control study. The genotype analysis of the AIB1 poly-Q repeat was conducted in 3,000 epithelial ovarian cancer (EOC) cases and 3,000 healthy controls. When analyzed as a categorical variable with cutoff of <28 or <29, both of results showed significant asociations. Compared to those with the shorter (<29) AIB1 poly-Q repeat length, women in the category of longer (≥29) poly-Q repeats had a significantly 20 % increased EOC risk (odds ratio (OR) = 1.20; 95 % confidence interval (CI), 1.08-1.33; P = 5.88 × 10(-4)). When analyzed as a continuous covariate, women with longer average poly-Q repeat length had a significantly increased risk of developing EOC (OR = 1.05 for per poly-Q repeat; 95 % CI, 1.00-1.08; P = 0.013). The association was more stronger for per longer allele (OR = 1.07; 95 % CI, 1.01-1.12; P = 0.010). These results strongly suggest that there is a significant effect of AIB1 genetic variation on ovarian cancer risk, and AIB1 underlies the development of ovarian cancer.