MP09-18 MISSENSE POLYMORPHISM IN SRD5A2 IN COMBINATION WITH HSD3B1 VARIATION IS ASSOCIATED WITH OUTCOME OF CASTRATION-RESISTANT PROSTATE CANCER PATIENTS TREATED WITH ABIRATERONE

Abstract

INTRODUCTION AND OBJECTIVE: Missense polymorphism in HSD3B1, encoding 3β-hydroxysteroid dehydrogenase-1, was associated with outcome after abiraterone treatment. However, the impact of missense polymorphism in SRD5A2 encoding 5α-reductase type 2 has not been reported. In this study, we investigated the significance of missense polymorphism in SRD5A2 gene and in combination with HSD3B1 variation in prostate cancer patients treated with abiraterone. METHODS: A total of 99 Japanese male castration-resistant prostate cancer patients treated with abiraterone between 2014 and 2018 were included. Genomic DNA was obtained from whole blood samples, and genotyping on SRD5A2 (rs523349, V89L) was performed by PCR-based technique. The association of HSD3B1 and SRD5A2 genotypes with clinicopathological parameters and oncological outcome, including treatment failure-free survival and overall survival, was examined. RESULTS: Among the 99 patients, 32 (32.3%), 49 (49.5%), and 18 patients (18.2%) carried GG, GC, and CC alleles in SRD5A2, respectively. CC allele was associated with lower risk of treatment failure (hazard ratio, 0.43; 95% confidence interval, 0.20–0.87; P = 0.017) on multivariate analyses, compared with GG/GC alleles (Fig. A). In the combination model using HSD3B1 and SRD5A2 polymorphisms, compared with the combination of AA in HSD3B1 and GG/GC in SRD5A2, other combinations were associated with lower risk of treatment failure (hazard ratio, 0.34; 95% confidence interval, 0.17–0.62; P = 0.0003) on multivariate analyses (Fig. B). CONCLUSIONS: This study showed that SRD5A2 genetic variation was associated with the risk of treatment failure in abiraterone. Combinational use of genetic variation in HSD3B1 with SRD5A2 genetic variation augmented the ability of prognostic stratification.Source of Funding: JSPS KAKENHI grant (17K11145)