Silvia Angelini1,2, Andrea Botticelli1, Concetta Elisa Onesti3,2, Raffaele Giusti2, Valentina Sini1,4, Valeria Durante1,2, Lidia Strigari5, Giovanna Gentile6, Bruna Cerbelli7, Patrizia Pellegrini2, Valentina Sgroi1,2, Mario Occhipinti1,2, Francesca Romana DI Pietro1,2, Alessandro Rossi8, Maurizio Simmaco9, Federica Mazzuca1,2, Paolo Marchetti1,2,6. 1. Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy. 2. Department of Medical Oncology, Sant'Andrea Hospital, Rome, Italy. 3. Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy elisaonesti@gmail.com. 4. Santo Spirito Hospital, Lungotevere in Saxia, Rome, Italy. 5. Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy. 6. Dermopatic Institute of the Immacolata IDI-IRCSS, Rome, Italy. 7. Department of Radiological Oncological and Pathological Sciences, "Sapienza" University of Rome, Rome, Italy. 8. Faculty of Medicine and Psychology, Sapienza" University of Rome, Rome, Italy. 9. Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), "Sapienza" University of Rome, Rome, Italy.
Abstract
BACKGROUND: Taxanes are widely used to treat breast cancer patients. Taxanes are metabolized in human liver by the cytochrome CYP3A and are substrate of ATP-binding cassette multidrug transporters ABCB1. Single-nucleotide polymorphisms (SNPs) in genes involved in taxanes' metabolism could affect the inter-individual variability in reported toxicities. MATERIALS AND METHODS: In this retrospective study, 152 women, affected by breast cancer and receiving a taxane-based chemotherapy, were enrolled. A peripheral blood sample was taken for genotyping the following polymorphisms: CYP3A4* 1B (A>G), CYP3A5 *3 (G>A) and ABCB1 (C1236T; C3435T). RESULTS: We observed an association between ABCB1 3435 T/T and lower grade of toxicities (p=0.05). No other association were found for CYP 3A4 *1B, 3A5*3 and ABCB1 C1236T. CONCLUSION: ABCB1 3435 T/T seems to be associated to lower rate of toxicity in patients receiving taxanes. Further prospective and larger studies should be performed to clarify the role of this polymorphism. Copyright
BACKGROUND:Taxanes are widely used to treat breast cancerpatients. Taxanes are metabolized in human liver by the cytochrome CYP3A and are substrate of ATP-binding cassette multidrug transporters ABCB1. Single-nucleotide polymorphisms (SNPs) in genes involved in taxanes' metabolism could affect the inter-individual variability in reported toxicities. MATERIALS AND METHODS: In this retrospective study, 152 women, affected by breast cancer and receiving a taxane-based chemotherapy, were enrolled. A peripheral blood sample was taken for genotyping the following polymorphisms: CYP3A4* 1B (A>G), CYP3A5 *3 (G>A) and ABCB1 (C1236T; C3435T). RESULTS: We observed an association between ABCB1 3435 T/T and lower grade of toxicities (p=0.05). No other association were found for CYP 3A4 *1B, 3A5*3 and ABCB1C1236T. CONCLUSION:ABCB1 3435 T/T seems to be associated to lower rate of toxicity in patients receiving taxanes. Further prospective and larger studies should be performed to clarify the role of this polymorphism. Copyright