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CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients treated with abiraterone

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Abstract

Background

Abiraterone became a standard hormonal therapy for patients with metastatic castration-resistance prostate cancer (mCRPC). However, patients may experience primary resistance to treatment. To date, few predictive biomarkers of efficacy have been identified. Our aim was to investigate the association between the single nucleotide polymorphism (SNP) c.-362T>C in the CYP17A1 gene, and clinical outcome in mCRPC patients treated with abiraterone.

Patients and methods

mCRPC patients candidate to receive abiraterone were enrolled in the present retrospective pharmacogenetic study. Based on a literature selection, CYP17A1 rs2486758 (c.-362T > C) was selected and analysed by real-time PCR on genomic DNA extracted from whole blood. Univariate analysis was performed to test the association between the SNP and treatment-related clinical outcomes.

Results

Sixty mCRPC patients were enrolled in the present study. Patients carrying the mutant CYP17A1 c.-362CT/CC genotypes showed a shorter median progression-free survival (PFS) and prostate-specific antigen-PFS (PSA-PFS) compared to patients carrying the TT genotype (10.7 vs 14.2 months and 8 vs 16 months, respectively; p = 0.04). No association between the selected SNP and the overall survival was found.

Conclusions

These findings suggest an association between CYP17A1 c.-362T>C polymorphism and poorer clinical outcome with abiraterone for mCRPC patients. However, further validations on larger cohort of patients are needed to confirm its role as a predictive biomarker for abiraterone resistance.

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Authors and Affiliations

  1. Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University Hospital of Pisa, 55, Via Roma, 56126, Pisa, Italy

    Stefania Crucitta, Marzia Del Re, Federico Cucchiara, Lorenzo Fontanelli & Romano Danesi

  2. Unit of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Federico Paolieri, Francesco Bloise, Andrea Sbrana, Enrico Sammarco, Chiara Mercinelli & Luca Galli

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  1. Stefania Crucitta
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Crucitta, S., Del Re, M., Paolieri, F. et al. CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients treated with abiraterone. Cancer Chemother Pharmacol 86, 527–533 (2020). https://doi.org/10.1007/s00280-020-04133-w

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