Prevalence and Prognostic Value of the Polymorphic Variant 1245A>C of HSD3B1 in Castration-resistant Prostate Cancer

Clin Genitourin Cancer. 2019 Oct;17(5):389-394. doi: 10.1016/j.clgc.2019.06.012. Epub 2019 Jun 26.

Abstract

Introduction: The purpose of this study was to investigate the prevalence and prognostic value of the polymorphic variant (1245A>C), a single nucleotide polymorphism (SNP) of the HSD3B1 gene, in the tumors of patients with castration-resistant prostate cancer (CRPC).

Materials and methods: We retrospectively evaluated 44 patients with CRPC who underwent palliative transurethral resection of the prostate. Genomic DNA was extracted from formalin-fixed and paraffin-embedded material, and 1245A>C SNP of the HSD3B1 gene was analyzed via Sanger sequencing. Cox regression analysis was used to assess the prognostic value of the respective SNP with time to progression as well as cancer-specific and overall survival in the subgroup of patients receiving second systemic treatment.

Results: The SNP was present in 20 patients (51.2%) who received second line systemic treatment additionally to androgen deprivation, of which 16 (80%) patients were heterozygous and 4 (20%) were homozygous. Correlation analysis revealed no association of the SNP with any clinical characteristics at initiation of second-line systemic treatment. Moreover, the presence of the variant (1245A>C) of HSD3B1 was not associated with any survival endpoint.

Conclusions: The variant allele 1245C of the HSD3B1 gene is present in approximately one-half of patients with CRPC; however, it is not associated with oncologic outcomes. These findings, however, need to be interpreted with caution as the sample size is small. Further research on biomarkers is needed to help tailor clinical decision making in prostate cancer, especially in the increasingly complex therapeutic landscape of CRPC.

Keywords: Biomarker; CRPC; Prognostic; SNP; Survival.

MeSH terms

  • Aged
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Combined Modality Therapy
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes / genetics*
  • Neoplasm Metastasis
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Progesterone Reductase / genetics*
  • Prognosis
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Prostatic Neoplasms, Castration-Resistant / therapy
  • Retrospective Studies
  • Steroid Isomerases / genetics*
  • Survival Rate
  • Transurethral Resection of Prostate

Substances

  • 3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
  • Androgen Antagonists
  • Biomarkers, Tumor
  • Multienzyme Complexes
  • Progesterone Reductase
  • Steroid Isomerases