Polymorphic Variants in NR1I3 and UGT2B7 Predict Taxane Neurotoxicity and Have Prognostic Relevance in Patients With Breast Cancer: A Case-Control Study.

Autor: Arbitrio M; CNR-Institute of Neurological Sciences, UOS of Pharmacology, Catanzaro, Italy., Scionti F; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy., Altomare E; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy., Di Martino MT; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy., Agapito G; Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Galeano T; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy., Staropoli N; Medical Oncology Unit, AOU Mater Domini, Catanzaro, Italy., Iuliano E; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy., Grillone F; Medical Oncology Unit, AOU Mater Domini, Catanzaro, Italy., Fabiani F; Medical Genetics Unit, AOU Mater Domini, Catanzaro, Italy., Caracciolo D; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy., Cannataro M; Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Arpino G; Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy., Santini D; Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy., Tassone P; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.; Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Tagliaferri P; Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.; Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2019 Aug; Vol. 106 (2), pp. 422-431. Date of Electronic Publication: 2019 Mar 28.
DOI: 10.1002/cpt.1391
Abstrakt: Taxane-related peripheral neuropathy (TrPN) is a dose-limiting toxicity with important interindividual variability. Genetic polymorphisms in absorption, distribution, metabolism, and excretion (ADME) genes may account for variability in drug efficacy and/or toxicity. By the use of Affymetrix drug-metabolizing enzyme and transporter microarray platform, in a retrospective case-control study, the correlation between ADME polymorphic variants and grades ≥ 2-3-TrPN was investigated. In a breast cancer (BC) training set, five single-nucleotide polymorphisms in NR1I3 and UDP-glucuronosyltransferase (UGT)2B7 genes were correlated to grades ≥ 2-3-TrPN protection. By receiver operating characteristic curves, the grades ≥ 2-3-TrPN-related candidate biomarkers in an independent series of 54 patients with BC (17 cases and 37 controls) were validated. NR1I3 was correlated to paclitaxel-TrPN and UGT2B7 to docetaxel-TrPN. Moreover, a genetic signature of prognostic relevance for BC outcome was found. Our findings might have potential relevance for personalized management of patients with BC for prevention of treatment failure in ultrametabolizer genetic variants.
(© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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