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Updated: May 14, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Genetic variants in AR and SHBG and resistance to hormonal castration in prostate cancer

Cátia Monteiro1, Marta Velho Sousa, Ricardo Ribeiro

  • 1Molecular Oncology Group-CI, Portuguese Institute of Oncology, Edificio Laboratorios-Piso 4, Rua Dr António Bernardino Almeida, 4200-072 Porto, Portugal. catiapmonteiro@gmail.com

Medical Oncology (Northwood, London, England)
|February 12, 2013
PubMed

Insights

Genetic variations in SHBG and AR genes impact prostate cancer patients' response to hormonal castration therapy. The SHBG +5790 G>A polymorphism is a potential marker for predicting resistance to treatment.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Prostate cancer patients with advanced disease can develop castration resistance after hormonal castration therapy (HCT).
  • Androgen receptor (AR) signaling and androgen bioavailability are implicated in the mechanisms of resistance to HCT.

Purpose of the Study:

  • To investigate the association between common functional polymorphisms in the AR and SHBG genes and the response to HCT in advanced prostate cancer patients.
  • To identify genetic markers that predict the development of castration resistance.

Main Methods:

  • Genomic DNA was isolated from 203 advanced prostate cancer patients treated with HCT.
  • Real-time PCR was used to determine the AR +1733 G>A and SHBG +5790 G>A genetic polymorphisms.
  • Genetic variants were analyzed for their association with treatment response and time to castration resistance.

Main Results:

  • Homozygous GG carriers of the SHBG +5790 G>A polymorphism showed an increased risk of developing castration resistance (HR = 1.9, P = 0.019).
  • A combined genetic profile including SHBG +5790 G>A and AR +1733 G>A also indicated a higher risk of resistance (HR = 1.9, P = 0.015).
  • These associations remained significant after adjusting for clinical factors like age, PSA, Gleason's score, and clinical stage.

Conclusions:

  • The SHBG +5790 G>A polymorphism may serve as a predictive marker for castration resistance in prostate cancer.
  • Pharmacogenomic profiling incorporating this SHBG polymorphism could aid in managing advanced prostate cancer patients undergoing HCT.

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