The CAG-triplet in the androgen receptor gene and single-nucleotide polymorphisms in androgen pathway genes in patients with concomitant bladder and prostate cancer.

Abstract

To test the hypothesis whether the number of the C(ytosine)-A(denine)-G(uanine) triplets in the androgen receptor (AR-) gene and further single-nucleotide polymorphisms in the androgen-responsive element of the promoter region of genes regulating the androgen pathway influence oncologic outcomes in patients with concomitant bladder (BC) and prostate cancer (PC) at a predisposing level. A cohort of 36 patients was treated with radical cystectomy and histologically exhibited invasive BC and incidental PC. The number of cytosine-adenine-guanine (CAG)-triplets (rs4045402) in the AR gene was assessed in tumor-free lymph nodes as well as rs743572 in the CYP17A1 gene and rs676033, rs523349, rs9282858 in the SRD5A2. In addition, the clinical significance of incidental PC based on the Epstein-criteria was assessed with regard to BC-specific recurrence-free survival (RFS). The median follow-up was 26 months (range: 4-68). Patients with clinically significant PC had worse BC-specific RFS compared with patients with insignificant PC (P = 0.016). Patients with a PC volume of >0.2 cm3 had shorter 3-year BC-specific RFS compared with patients with a PC volume ≤0.2 cm3 (P = 0.025). The median number of CAG-triplets was 24 (mean ± SEM: 23 ± 2, interquartile range: 22-25, total range 18-29). Patients with a CAG-triplet number <23 exhibited significantly decreased 3-year BC specific RFS compared with patients with ≥23 repeats (27% vs. 65%; P = 0.026). No further significance were noted for the other tested SNPs and survival. A detailed description of incidental PC at radical cystoprostatectomy (RC) may be of greater prognostic importance than previously assumed in the literature. The CAG-repeat in the AR gene may predispose to worse oncologic outcomes after RC and should be further evaluated in larger studies.