AIB1 polymorphisms predict aggressive ovarian cancer phenotype

Purpose: The androgen receptor (AR) harbors a polymorphic CAG repeat sequence in exon 1, coding for a polyglutamine tract whose length inversely correlates with AR transactivation function. AIB1, an AR coactivator, expresses a similar polymorphic glutamine 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 genotype on clinical outcome. Experimental Design: Genotype analysis of the AIM CAG repeat region was done on 89 patients with epithelial ovarian cancer. Medical records were reviewed for clinicopathologic factors and survival. Data were examined using the chi(2) test and Kaplan-Meier survival and Cox regression analyses. Results: We identified four AIB1 genotypes, with glutamine codon lengths of 26, 28, 29, and 30. Patients with a short AIB1 genotype (with <= 28 CAG repeats) showed statistically shorter time to disease recurrence compared to those with a long genotype (>= 29 CAG repeats; 15.0 versus 30.0 months; P = 0.01). Patients with short AIB1 also showed decreased overall survival (57.0 months) compared to those with a long genotype (median survival not yet reached; P = 0.02). When controlling for established prognostic factors, multivariate analysis identified the presence of a short AIB1 genotype as an independent poor prognostic factor for overall survival (P = 0.05). Conclusions: These data suggest that short AIB1 genotypes may promote aggressive malignant phenotypes of epithelial ovarian cancer.