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Association of Glutathione S-Transferase P-1 (GSTP-1) rs1695 polymorphism with overall survival in glioblastoma patients treated with combined radio-chemotherapy

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Summary

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m2 during RT and 200 mg/m2 days 1 → 5 every 28 days) were enrolled. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between curves. A trend to a statistically significant association with PFS in univariate and multivariate COX regression analysis was found with GSTP-1 rs1695 polymorphism (p = 0.087 and p = 0.097 on univariate and multivariate analyses, respectively). Conversely, the same GSTP-1 rs1695 SNP revealed a statistically significant association with OS (p = 0.007 and p = 0.042 on univariate and multivariate analysis, respectively). Our pharmacogenetic prospective study suggests that GSTP-1 rs1695 genotypes can be associated with different OS in GBM patients treated with RT and TMZ.

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Acknowledgements

The authors wish to thank patients and their families for their participation to the study, which was funded, in part, by the Fondazione Arpa through the “Progetto Luca Gambicorti” to FP , and by the University of Pisa through the “Fondi di Ateneo” to GB. The author thank Prof. Giulio Francia for help with editing the text.

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Authors and Affiliations

  1. Division of Radiation Oncology, Department of Oncology, Pisa University Hospital, Pisa, Italy

    Francesco Pasqualetti, Alessandra Gonnelli, Martina Cantarella, Durim Delishaj, Alessandro Molinari, Sabrina Montrone, Stefano Ursino & Fabiola Paiar

  2. Division of Surgical, Molecular and Ultrastructural Pathology, University of Pisa, Pisa, Italy

    Valerio Ortenzi, Francesco Carbone & Antonio Giuseppe Naccarato

  3. Fondazione Pisana per la Scienza, Pisa, Italy

    Sara Franceschi & Chiara Maria Mazzanti

  4. Section of Statistics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Riccardo Morganti

  5. Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56125, Pisa, Italy

    Paola Orlandi, Teresa Di Desidero & Guido Bocci

  6. Department of Translational Research and of New Surgical and Medical Technologies, Pisa University Hospital, Pisa, Italy

    Katia Zavaglia

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  1. Francesco Pasqualetti
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Correspondence to Guido Bocci.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Pasqualetti, F., Gonnelli, A., Cantarella, M. et al. Association of Glutathione S-Transferase P-1 (GSTP-1) rs1695 polymorphism with overall survival in glioblastoma patients treated with combined radio-chemotherapy. Invest New Drugs 36, 340–345 (2018). https://doi.org/10.1007/s10637-017-0516-2

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  • DOI: https://doi.org/10.1007/s10637-017-0516-2

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