Germline HSD3B1 Genetics and Prostate Cancer Outcomes.

Lewis Thomas, Nima Sharifi

Journal: Urology 2022;145():13-21

PMID: 32866512

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Abstract

Dihydrotestosterone synthesis in prostate cancer from adrenal DHEA/DHEA-sulfate requires enzymatic conversion in tumor tissues. 3β-hydroxysteroid dehydrogenase-1 is an absolutely necessary enzyme for such dihydrotestosterone synthesis and is encoded by the gene HSD3B1 which comes in 2 functional inherited forms described in 2013. The adrenal-permissive HSD3B1(1245C) allele allows for rapid dihydrotestosterone synthesis. The adrenal-restrictive HSD3B1(1245A) allele limits androgen synthesis. Studies from multiple cohorts show that adrenal-permissive allele inheritance confers worse outcomes and shorter survival after castration in low-volume prostate cancer and poor outcomes after abiraterone or enzalutamide treatment for castration-resistant prostate cancer. Here, we review the clinical data and implications.

Address: Genitourinary Malignancies Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.; Genitourinary Malignancies Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address: [email protected].

DOI: 10.1016/j.urology.2020.08.028

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MeSH Terms: Androgen Antagonists, Germ Cells, Humans, Male, Multienzyme Complexes, Progesterone Reductase, Prostatic Neoplasms, Steroid Isomerases, Treatment Outcome