Investigational New Drugs

, Volume 36, Issue 2, pp 340–345 | Cite as

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

  • Francesco Pasqualetti
  • Alessandra Gonnelli
  • Martina Cantarella
  • Durim Delishaj
  • Alessandro Molinari
  • Valerio Ortenzi
  • Francesco Carbone
  • Sabrina Montrone
  • Stefano Ursino
  • Sara Franceschi
  • Riccardo Morganti
  • Paola Orlandi
  • Teresa Di Desidero
  • Chiara Maria Mazzanti
  • Katia Zavaglia
  • Antonio Giuseppe Naccarato
  • Guido Bocci
  • Fabiola Paiar
SHORT REPORT

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.

Keywords

GSTP-1 rs1695 Single nucleotide polymorphism Glioblastoma Radiotherapy Chemotherapy 

Notes

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.

Compliance with ethical standards

Conflict of interest

Authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, Chinot O, Ram Z, Reifenberger G, Soffietti R, Wick W, European Association for Neuro-Oncology (EANO) Task Force on Malignant Glioma (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15(9):e395–e403CrossRefPubMedGoogle Scholar
  2. 2.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMedGoogle Scholar
  3. 3.
    Soffietti R, Trevisan E, Bertero L, Cassoni P, Morra I, Fabrini MG, Pasqualetti F, Lolli I, Castiglione A, Ciccone G, Rudà R (2014) Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology). J Neuro-Oncol 116(3):533–541CrossRefGoogle Scholar
  4. 4.
    Omuro A, DeAngelis LM (2013) Glioblastoma and other malignant gliomas: a clinical review. JAMA 310(17):1842–1850CrossRefPubMedGoogle Scholar
  5. 5.
    Chinot OL, de La Motte RT, Moore N, Zeaiter A, Das A, Phillips H, Modrusan Z, Cloughesy T (2011) AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Ther 28(4):334–340CrossRefPubMedGoogle Scholar
  6. 6.
    Eisele G, Wick A, Eisele AC, Clément PM, Tonn J, Tabatabai G, Ochsenbein A, Schlegel U, Neyns B, Krex D, Simon M, Nikkhah G, Picard M, Stupp R, Wick W, Weller M (2014) Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. J Neuro-Oncol 117(1):141–145CrossRefGoogle Scholar
  7. 7.
    Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D, Steinbach JP, Wick W, Tarnawski R, Nam DH, Hau P, Weyerbrock A, Taphoorn MJ, Shen CC, Rao N, Thurzo L, Herrlinger U, Gupta T, Kortmann RD, Adamska K, McBain C, Brandes AA, Tonn JC, Schnell O, Wiegel T, Kim CY, Nabors LB, Reardon DA, van den Bent MJ, Hicking C, Markivskyy A, Picard M, Weller M, European Organisation for Research and Treatment of Cancer (EORTC), Canadian Brain Tumor Consortium, CENTRIC study team (2014). Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 15(10): 1100–1108Google Scholar
  8. 8.
    Sharma RA, Plummer R, Stock JK, Greenhalgh TA, Ataman O, Kelly S, Clay R, Adams RA, Baird RD, Billingham L, Brown SR, Buckland S, Bulbeck H, Chalmers AJ, Clack G, Cranston AN, Damstrup L, Ferraldeschi R, Forster MD, Golec J, Hagan RM, Hall E, Hanauske AR, Harrington KJ, Haswell T, Hawkins MA, Illidge T, Jones H, Kennedy AS, McDonald F, Melcher T, O'Connor JP, Pollard JR, Saunders MP, Sebag-Montefiore D, Smitt M, Staffurth J, Stratford IJ, Wedge SR; NCRI CTRad Academia-Pharma Joint Working Group (2016). Clinical development of new drug-radiotherapy combinations. Nat Rev Clin Oncol 13(10): 627–642Google Scholar
  9. 9.
    Thacker J, Zdzienicka MZ (2003) The mammalian XRCC genes: their roles in DNA repair and genetic stability. DNA Repair (Amst) 2(6):655–672CrossRefGoogle Scholar
  10. 10.
    Thacker J, Zdzienicka MZ (2004) The XRCC genes: expanding roles in DNA double-strand break repair. DNA Repair (Amst) 3(8–9):1081–1090CrossRefGoogle Scholar
  11. 11.
    Shridhar K, Aggarwal A, Walia GK, Gulati S, Geetha AV, Prabhakaran D, Dhillon PK, Rajaraman P (2016) Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date. Oral Oncol 61:146–151CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sun JF, Sui JL, Zhou PK, Geng Y, Hu YC, Cao ZS, Ge SL, Lou TZ, Wu DC (2002) Decreased efficiency of gamma-ray-induced DNA double-strand break rejoining in malignant transformants of human bronchial epithelial cells generated by alpha-particle exposure. Int J Radiat Biol 78(9):773–780CrossRefPubMedGoogle Scholar
  13. 13.
    Gal TJ, Huang WY, Chen C, Hayes RB, Schwartz SM (2005) DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients. Laryngoscope 115(12):2221–2231CrossRefPubMedGoogle Scholar
  14. 14.
    Jin H, Xie X, Wang H, Hu J, Liu F, Liu Z, Zhou J, Zhang Y, Xi X, Hu B, Liao Y, Tang J (2014) ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma. PLoS One 9(7):e101256CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhai XM, Hu QC, Gu K, Wang JP, Zhang JN, Wu YW (2016) Significance of XRCC1 Codon399 polymorphisms in Chinese patients with locally advanced nasopharyngeal carcinoma treated with radiation therapy. Asia Pac J Clin Oncol 12(1):e125–e132CrossRefPubMedGoogle Scholar
  16. 16.
    Tew KD (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res 54(16):4313–4320PubMedGoogle Scholar
  17. 17.
    Tew KD, Manevich Y, Grek C, Xiong Y, Uys J, Townsend DM (2011) The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer. Free Radic Biol Med 51(2):299–313CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Prade L, Huber R, Manoharan TH, Fahl WE, Reuter W (1997) Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor. Structure 5(10):1287–1295CrossRefPubMedGoogle Scholar
  19. 19.
    Hu X, Xia H, Srivastava SK, Herzog C, Awasthi YC, Ji X, Zimniak P, Singh SV (1997) Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun 238(2):397–402CrossRefPubMedGoogle Scholar
  20. 20.
    Ishimoto TM, Ali-Osman F (2002) Allelic variants of the human glutathione S-transferase P1 gene confer differential cytoprotection against anticancer agents in Escherichia coli. Pharmacogenetics 12(7):543–553CrossRefPubMedGoogle Scholar
  21. 21.
    Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9(5):453–461CrossRefPubMedGoogle Scholar
  22. 22.
    Qi L, Yu HQ, Zhang Y, Ding LJ, Zhao DH, Lv P, Wang WY, Xu Y (2017) A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk. Mol Neurobiol 54(2):1314–1325CrossRefPubMedGoogle Scholar
  23. 23.
    Rapkins RW, Wang F, Nguyen HN, Cloughesy TF, Lai A, Ha W, Nowak AK, Hitchins MP, McDonald KL (2015) The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide. Neuro-Oncology 17(12):1589–1598CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Franceschi S, Tomei S, Mazzanti CM, Lessi F, Aretini P, La Ferla M, De Gregorio V, Pasqualetti F, Zavaglia K, Bevilacqua G, Naccarato AG (2016) Association between RAD 51 rs1801320 and susceptibility to glioblastoma. J Neuro-Oncol 126(2):265–270CrossRefGoogle Scholar
  25. 25.
    Pasqualetti F, Orlandi P, Simeon V, Cantarella M, Giuliani D, Di Desidero T, Gonnelli A, Delishaj D, Lombardi G, Sechi A, Sanson M, Zagonel V, Paiar F, Danesi R, Guarini S, Bocci G (2017) Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy. Mol Neurobiol.  https://doi.org/10.1007/s12035-017-0414-9
  26. 26.
    Sullivan I, Salazar J, Majem M, Pallarés C, Del Río E, Páez D, Baiget M, Barnadas A (2014) Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Cancer Lett 353(2):160–166CrossRefPubMedGoogle Scholar
  27. 27.
    Leguisamo NM, Gloria HC, Kalil AN, Martins TV, Azambuja DB, Meira LB, Saffi J (2017). Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy. Oncotarget 8(33):54199-54214Google Scholar
  28. 28.
    Muñoz C, Caballero M, Hakim S, Verger E, Grau JJ (2016) Influence of allelic Variations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab. Eur Arch Otorhinolaryngol 273(8):2193–2199CrossRefPubMedGoogle Scholar
  29. 29.
    Liu HF, Liu JS, Deng JH, Wu RR (2016) Role of XRCC1 gene polymorphisms in non-small cell lung cancer cisplatin-based chemotherapy, and their effect on clinical and pathological characteristics. Genet Mol Res 15(4).  https://doi.org/10.4238/gmr15049084
  30. 30.
    Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Francesco Pasqualetti
    • 1
  • Alessandra Gonnelli
    • 1
  • Martina Cantarella
    • 1
  • Durim Delishaj
    • 1
  • Alessandro Molinari
    • 1
  • Valerio Ortenzi
    • 2
  • Francesco Carbone
    • 2
  • Sabrina Montrone
    • 1
  • Stefano Ursino
    • 1
  • Sara Franceschi
    • 3
  • Riccardo Morganti
    • 4
  • Paola Orlandi
    • 5
  • Teresa Di Desidero
    • 5
  • Chiara Maria Mazzanti
    • 3
  • Katia Zavaglia
    • 6
  • Antonio Giuseppe Naccarato
    • 2
  • Guido Bocci
    • 5
  • Fabiola Paiar
    • 1
  1. 1.Division of Radiation Oncology, Department of OncologyPisa University HospitalPisaItaly
  2. 2.Division of Surgical, Molecular and Ultrastructural PathologyUniversity of PisaPisaItaly
  3. 3.Fondazione Pisana per la ScienzaPisaItaly
  4. 4.Section of Statistics, Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  5. 5.Division of Pharmacology, Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  6. 6.Department of Translational Research and of New Surgical and Medical TechnologiesPisa University HospitalPisaItaly

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