Association of HSD3B1 rs1047303 polymorphism with prognosis in metastatic prostate cancer: A systematic review and meta-analysis

Background The HSD3B1 rs1047303 (1245A > C) polymorphism encodes a gain-of-function variant in 3β-hydroxysteroid dehydrogenase-1 that enhances extragonadal androgen synthesis. Conflicting evidence exists regarding the prognostic value of the polymorphism in metastatic prostate cancer. Methods We systematically searched PubMed, Web of Science, and Embase for studies evaluating the association between HSD3B1 rs1047303 genotype and clinical outcomes in metastatic prostate cancer. We pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) using random-effects models. Subgroup analyses were conducted to assess the prognostic association of the polymorphism in patients with metastatic castration-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC), respectively. Results Nine studies involving 1947 patients were included. In mHSPC, the variant genotype was associated with significantly worse overall survival (OS) (pooled HR = 1.49, 95% CI: 1.15–1.92, P = 0.002; I 2 = 11%) and worse progression-free survival (PFS) (pooled HR = 1.69, 95% CI: 1.15–2.49, P = 0.008; I 2 = 61%). In mCRPC, neither OS (pooled HR = 1.01, 95% CI: 0.33–3.15, P = 0.98; I 2 = 76%) nor PFS (pooled HR = 1.06, 95% CI: 0.31–3.59, P = 0.93; I 2 = 85%) was significantly associated with genotype. Conclusions This meta-analysis suggests that the HSD3B1 rs1047303 variant is associated with worse survival in mHSPC, supporting its potential as a prognostic biomarker. In mCRPC, the prognostic value remains inconclusive. Given the observational nature of the included studies, these findings are hypothesis-generating and require prospective validation.