Evaluation of the impact of SRD5A2 polymorphism on dutasteride response in patients with bladder cancer

Dutasteride is an orally administered drug and shows its effect by inhibiting both the type-1 and type-2 isoenzymes of the 5-alpha reductase enzyme which converts testosterone to dihydrotestosterone. It is known that V89L (rs523349) and A49T (rs9282858) polymorphisms, which are the most common variations on the SRD5A2 gene encoding the 5-alpha reductase enzyme, affect the enzyme activity. The aim of the study was to investigate the impact of SRD5A2 gene polymorphisms on the efficacy and safety of dutasteride in patients with bladder cancer receiving dutasteride treatment in a phase 2 clinical trial. DNAs were isolated from blood samples taken from 22 patients and polymerase chain reaction (PCR) was established. Using the TaqMan SNP Genotyping Assay system, single nucleotide polymorphisms on DNA were detected by amplification. Analyzes were performed using the Applied Biosystems Instruments 7500 Fast Real-Time PCR Systems (Applied Biosystems™) PCR instrument, TaqMan Genotype Software Version 1.6.0 (Applied Biosystems™) and Microsoft Excel programs. Causal relation between dutasteride use and the adverse events and severity of them was evaluated. All statistical analyzes were performed with the Statistical Package for the Social Sciences (SPSS, Inc., Chicago IL), version 22, Windows software, and p<0.05 was considered statistically significant. All patients were homozygous GG (100%) for the V89L polymorphism in the SRD5A2 gene; In terms of A49T (rs9282858) polymorphism, 11 of 22 patients were heterozygous TC (50%), 9 homozygous TT (40.9%), and 1 homozygous CC (4.5%). There was no statistically significant difference between different genotypes of A49T polymorphism and disease recurrence (p=0.715). None of these events were causally related to dutasteride use. To best of our knowledge, this study is the first to reveal the frequency of V89L and A49T polymorphisms on the SRD5A2 gene of patients with bladder cancer and to investigate its relationship with bladder cancer recurrence. In order to investigate the impact of SRD5A2 gene polymorphisms on the efficacy and safety of dutasteride, studies with much larger sample size and the control group are needed.