The association between genetic variants in HSD3B1 and clinical management of PCa

Abstract

Androgen is an important factor in the occurrence and progression of prostate cancer. The principal clinical strategy is androgen deprivation therapy (ADT). However, progression to castrate-resistant prostate cancer (CRPC) is almost inevitable to occur after ADT. One of the key mechanisms is the intertumoral synthesis of androgen where 3β-hydroxysteroid dehydrogenase isoenzyme-1 (3βHSD1, encoded by HSD3B1) catalyzes the rate-limiting step. A germline missense-encoding variant of HSD3B1(1245A>C, rs1047303) has been the focus of research because HSD3B1(1245C) works as an adrenal-permissive allele and encodes a more stable enzyme that promotes the synthesis of androgen. Several studies were performed to explore the role of HSD3B1(1245C) in the development of CRPC and the outcome of clinical management. Thus, we searched the published research articles using the keywords “prostate cancer” and “HSD3B1”, in PubMed and Embase database. After reviewing the abstracts and full articles, 16 original research articles from 45 search results were finally selected and reviewed. Based on the current evidence, HSD3B1(1245C) is proposed to accelerate ADT resistance and the development of CRPC. It is also associated with a poorer prognosis of PCa treated with ADT. However, due to conflicting results, the association between HSD3B1(1245C) and the effect of next-generation hormone therapy (i.e., abiraterone) for patients with CRPC is not clear enough. In conclusion, HSD3B1(1245C) has value for predicting the outcome of PCa and potential to be involved in therapeutic decision making.

Keywords

HSD3B1 / germline / prostate cancer / androgen deprivation therapy / castration-resistant prostate cancer / abiraterone / predictive biomarker / multienzyme complexes / patient stratification / omics

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