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

The document reviewed the impact of the HSD3B1 gene, particularly the 1245 A→C polymorphism, on the progression of castration-resistant prostate cancer (CRPC) and other conditions. It was found that the adrenal-permissive HSD3B1(1245C) genotype is associated with poorer outcomes after androgen deprivation therapy in prostate cancer, with a study of 213 men showing a significant decrease in metastasis-free survival for those with the homozygous adrenal-permissive allele. The genotype also affects the efficacy of abiraterone treatment in prostate cancer, with mixed results. Beyond prostate cancer, the HSD3B1(1245C) allele was negatively associated with mammographic density and positively associated with androgenic alopecia, especially in overweight women with polycystic ovarian syndrome. The document also mentioned inconclusive associations with hypertension and benign prostatic hyperplasia and suggested that HSD3B1 genotype status might influence the outcomes of DHEA supplementation, recommending that future trials consider ancestry and genotype status. Financial support and potential conflicts of interest were disclosed.