Germline HSD3B1 Genetics and Prostate Cancer Outcomes

Lewis Thomas; Nima Sharifi

doi:10.1016/j.urology.2020.08.028

Germline HSD3B1 Genetics and Prostate Cancer Outcomes

Lewis Thomas, Nima Sharifi

Research output: Contribution to journal › Review article › peer-review

24 Scopus citations

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.

Original language	English
Pages (from-to)	13-21
Number of pages	9
Journal	Urology
Volume	145
DOIs	https://doi.org/10.1016/j.urology.2020.08.028
State	Published - Nov 2020

Access to Document

10.1016/j.urology.2020.08.028

Cite this

@article{0fbdbfd493374af386fc33f31fb841f7,

title = "Germline HSD3B1 Genetics and Prostate Cancer Outcomes",

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.",

author = "Lewis Thomas and Nima Sharifi",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = nov,

doi = "10.1016/j.urology.2020.08.028",

language = "English",

volume = "145",

pages = "13--21",

journal = "Urology",

issn = "0090-4295",

}

TY - JOUR

T1 - Germline HSD3B1 Genetics and Prostate Cancer Outcomes

AU - Thomas, Lewis

AU - Sharifi, Nima

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85091524462&partnerID=8YFLogxK

U2 - 10.1016/j.urology.2020.08.028

DO - 10.1016/j.urology.2020.08.028

M3 - Review article

C2 - 32866512

AN - SCOPUS:85091524462

SN - 0090-4295

VL - 145

SP - 13

EP - 21

JO - Urology

JF - Urology

ER -

Germline HSD3B1 Genetics and Prostate Cancer Outcomes

Abstract

Access to Document

Other files and links

Fingerprint

Cite this