HSD3B1 Genotypes Conferring Adrenal-Restrictive and Adrenal-Permissive Phenotypes in Prostate Cancer and Beyond.

ABSTRACT: Castration-resistant prostate cancer (PCa) almost invariably occurs after androgen deprivation therapy for metastatic disease and is driven in part by androgen synthesis within the tumor. 3β-hydroxysteroid dehydrogenase isoenzyme-1 catalyzes the conversion of adrenal precursor steroids into potent androgens essential for PCa progression. A common 1245 A→C missense-encoding single nucleotide polymorphism in HSD3B1 (rs1047303), the gene that encodes this enzyme, leads to a more stable protein that is resistant to degradation and thus increased production of potent androgens from adrenal precursors, facilitating castration-resistant PCa development. Consistent with this mechanism, this adrenal-permissive HSD3B1(1245C) genotype is associated with inferior outcomes after androgen deprivation th

SUBMITTER: Sabharwal N 

PROVIDER: S-EPMC6736215 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature