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  • Title: Impact of androgen receptor cytosine-adenine-guanine polymorphisms on clinical outcome in BRCA mutation-associated epithelial ovarian cancers.
    Author: Li AJ, McAllister P, Karlan BY.
    Journal: Gynecol Oncol; 2010 Jan; 116(1):105-8. PubMed ID: 19818997.
    Abstract:
    PURPOSE: Androgen signaling may function in the pathobiology of epithelial ovarian cancers associated with mutations in the BRCA1/2 genes. Androgen receptor (AR) activity correlates inversely with length of a polymorphic cytosine-adenine-guanine (CAG) repeat in exon 1. We hypothesized that AR CAG allele length is a modifier of clinical outcome in BRCA1/2 mutation positive women with ovarian cancer. EXPERIMENTAL DESIGN: We identified BRCA1/2 ovarian cancer patients with banked serum from which we PCR amplified the CAG repeat region. We abstracted clinical and survival data, and examined CAG repeat length <19 as a short AR allelotype. We calculated a sample size of 60 patients to determine a 24-month difference in survival. RESULT: In 62 patients, 43 (69%) had BRCA1 mutations and 19 (31%) had BRCA2 mutations. Fifteen (24%) were found to have a short AR allelotype. Patients with a short AR did not demonstrate statistical differences in progression-free survival (43 months vs. 28 months for long AR) or overall survival (78 months vs. 142 months for long AR). In patients with BRCA2 mutations alone, a short AR correlated with decreased overall survival (31 months) compared to 126 months for those with a long AR (p=0.01). CONCLUSIONS: AR allelotype length did not correlate with survival in this statistically representative cohort of patients with BRCA1/2 mutations. Potential associations between short AR and outcome in BRCA2-associated ovarian cancers remain to be determined.
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