CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients
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ORIGINAL ARTICLE
CYP17A1 polymorphism c.‑362T>C predicts clinical outcome in metastatic castration‑resistance prostate cancer patients treated with abiraterone Stefania Crucitta1 · Marzia Del Re1 · Federico Paolieri2 · Francesco Bloise2 · Andrea Sbrana2 · Enrico Sammarco2 · Chiara Mercinelli2 · Federico Cucchiara1 · Lorenzo Fontanelli1 · Luca Galli2 · Romano Danesi1 Received: 2 May 2020 / Accepted: 22 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords CYP17A1 · Polymorphism · CRPC · Abiraterone · Pharmacogenetics
Introduction Prostate cancer is the most commonly diagnosed cancer among men in Western countries, accounting for 24% of all new cancers diagnosed in 2018, and is considered as the second and third leading cause of cancer death in American and European men, respectively [1–3]. Although the incidence of prostate cancer is high, most of the cases are * Marzia Del Re [email protected] 1
Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University Hospital of Pisa, 55, Via Roma, 56126 Pisa, Italy
Unit of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
2
detected when the cancer is localised within the prostate, with a 5-year survival rate in USA of 98% [3]. The rate of patients with metastatic prostate cancer at diagnosis is less than 30% and remains low [4]. Metastatic prost
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