The Association Between Hsd3b1 Genotype And Steroid Metabolism In Normal And Prostate Cancer (Pca) Tissue.

TPS155Background: The common germline variant HSD3B1(1245C) encodes for a gain-of-function in 3βHSD1 which is associated with a shorter duration of response to androgen deprivation therapy (ADT) and more rapid disease progression to castration resistant PCa (CRPC) as shown previously in 5 independent cohorts. Therefore, evaluating the effect of such genotype variation on the level of steroid metabolites and the intratumoral dihydrotestosterone (DHT) concentration in benign and tumor tissue of men on ADT is of significant importance. We hypothesize that patients with homozygous HSD3B1 (1245C) genotype (HZ) will have a sustained androgen synthesis from extragonadal precursor steroids and higher concentrations of DHT compared to patients with wild-type HSD3B1 (1245A) (WT) inheritance in the context of testosterone suppression. In addition, it is expected that heterozygous HSD3B1 (1245C) patients (HTZ) will have intermediate levels of DHT. We also hypothesize that treatment with androgen receptor (AR) antagon...