Adrenal-Permissive Germline HSD3B1 Allele and Prostate Cancer Outcomes.

Importance: The adrenal androgen-metabolizing 3β-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1(1245C) allele is responsible for encoding the 3β-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer.

Association between prediagnostic prostate-specific antigen and prostate cancer probability in Black and non-Hispanic White men.

Background: Although Black men are more likely than non-Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate-specific antigen (PSA) screening protocols in Black men. This study investigated whether the risk for prostate cancer was higher than expected among self-identified Black than White veterans based on prebiopsy PSA level.

Methods: Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans.

Development and Validation of a Tool to Identify Patients Diagnosed With Castration-Resistant Prostate Cancer.

Purpose: Several novel therapies for castration-resistant prostate cancer (CRPC) have been approved with randomized phase III studies with continuing observational research either planned or ongoing. Accurately identifying patients with CRPC in electronic health care data is critical for quality observational research, resource allocation, and quality improvement. Previous work in this area has relied on either structured laboratory results and medication data or natural language processing (NLP) methods.

Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program.

Background: Genetic scores may provide an objective measure of prostate cancer risk and thus inform screening decisions. We evaluated whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with prostate cancer risk in a diverse population, including Black men, who have higher average risk of prostate cancer death but are often treated as a homogeneously high-risk group.

Methods: This was a retrospective analysis of the Million Veteran Program, a national, population-based cohort study of US military veterans conducted 2011-2021.