Presentation Authors: Georgios Gakis*, Tina Schubert, Würzburg, Germany, Maritta Munz, Arnulf Stenzl, Markus Renninger, Tübingen, Germany
Introduction: There is evidence in literature which suggests that the androgen signaling pathway may exert an adverse impact on outcomes of patients with bladder cancer (BC) which may be further pronounced in those with concomitant prostate cancer (PC). Therefore, the objective of the study was to investigate the predisposing role of the activity of the androgen receptor (AR-) gene and single-nucleotide polymorphisms (SNPs) in androgen-regulated genes in patients with concomitant BC and PC.
Methods: A total of 792 genotyping analyses were conducted in 36 patients with invasive BC and incidental PC treated with radical cystoprostatectomy (RCP) between 2003 and 2008. DNA was isolated from tumor-free lymphatic tissue derived from lymph node dissection during RCP and amplified by PCR analysis. Following this, DNA sequencing was conducted to determine the specific allelic variants. Twenty-one risk SNPs located in androgen-responsive elements of the promoter region of the following genes were investigated: PSCA (rs2978974, rs2294008, rs3736001, rs1045531), NAT1 (rs15561), MYC (rs6983267), CYP17A1 (rs743572), SDR5A2 (rs676033, rs523349, rs9285858), ALPK1 (rs2051778), ARRDC3 (rs2939244), BMP5 (3734444), CASP3 (rs4862396), FBXO32 (rs7830622), FLT1 (rs9508016), IRS2 (rs7986346), SKAP1 (rs6504145), TACC2 (rs3763763), MIR151A (rs14974929) and BCN2 (rs16934641). In addition, the number of Cytosine-Adenine-Guanine (CAG) triplets in the AR gene was measured which is inversely related to the activity of the gene. Histopathologic parameters of patients were correlated with genetic findings and Kaplan-Meier analyses were conducted to evaluate the impact of the risk alleles on 3-year BC recurrence-free survival. The median follow-up was 41 months (range: 3-102).
Results: The mean number Â± S.E.M of CAG-triplets in the AR gene was 23Â±2 (median: 24, IQR: 22-25, total range: 18-29). The presence of the rs15561 was associated with â‰¥pT3a stage at RCP (p=0.030). Lymph node positive disease was associated with the rs2051778 (p=0.020). A lower number of CAG-repeats in the AR-gene (â‰¥23 vs. â‰¤22) was significantly associated with inferior RFS (27% vs. 65%; p=0.026). RFS was also significantly lower in patients with the rs2978974 allele (32% vs. 75%; p=0.015) and in those with the risk SNP rs15561 (28% vs. 65%; p=0.019).
Conclusions: These data suggest that the activity of AR gene and the specific risk SNPs in androgen-regulated genes act as predisposing factors on outcomes on patients with concomitant BC and PC.