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Huang et al. J Transl Genet Genom 2021;5:240-9 Journal of Translational
DOI: 10.20517/jtgg.2021.14
Genetics and Genomics

Review Open Access

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

1
1
Jingyi Huang , Da Huang , Rong Na 1,2
1
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
2
Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL 60201, USA.
Correspondence to: Dr. Rong Na, Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197
Ruijin 2nd Road, Shanghai 200025, China. E-mail: narong.hs@gmail.com; Dr. Da Huang, Department of Urology, Ruijin Hospital,
Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
E-mail: huangdasjtu@gmail.com

How to cite this article: Huang J, Huang D, Na R. The association between genetic variants in HSD3B1 and clinical management
of PCa. J Transl Genet Genom 2021;5:240-9. https://dx.doi.org/10.20517/jtgg.2021.14
Received: 13 Mar 2021 First Decision: 25 May 2021 Revised: 7 Jun 2021 Accepted: 11 Jun 2021 First online: 17 Jun 2021

Academic Editor: Sanjay Gupta Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

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.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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