Germline HSD3B1 Genetics and Prostate Cancer Outcomes

Lewis Thomas, Nima Sharifi

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations


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.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
StatePublished - Nov 2020


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