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Association between RAD 51 rs1801320 and susceptibility to glioblastoma

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Abstract

Glioblastoma is the most common and aggressive malignant primary brain tumor. Despite decades of research and the advent of new therapies, patients with glioblastoma continue to have a very poor prognosis. Radiation therapy has a major role as adjuvant treatment for glioblastoma following surgical resection. Many studies have shown that polymorphisms of genes involved in pathways of DNA repair may affect the sensitivity of the cells to treatment. Although the role of these polymorphisms has been investigated in relation to response to radiotherapy, their role as predisposing factors to glioblastoma has not been clarified yet. In the present study, we evaluated the association between polymorphisms in DNA repair genes, namely: XRCC1 rs25487, XRCC3 rs861539 and RAD51 rs1801320, with the susceptibility to develop glioblastoma. Eighty-five glioblastoma patients and 70 matched controls were recruited for this study. Data from the 1000 Genomes Project (98 Tuscans) were also downloaded and used for the association analysis. Subjects carrying RAD51 rs1801320 GC genotype showed an increased risk of glioblastoma (GC vs GG, χ2 = 10.75; OR 3.0087; p = 0.0010). The C allele was also significantly associated to glioblastoma (χ2 = 8.66; OR 2.5674; p = 0.0032). Moreover, RAD51 rs1801320 C allele increased the risk to develop glioblastoma also when combined to XRCC1 rs25487 G allele and XRCC3 rs861539 C allele (χ2 = 6.558; p = 0.0053).

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References

  1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109

    Article  PubMed  PubMed Central  Google Scholar 

  2. Le Mercier M, Hastir D, Moles Lopez X, De Nève N, Maris C, Trepant AL, Rorive S, Decaestecker C, Salmon I (2012) A Simplified Approach for the Molecular Classification of Glioblastomas. PLoS ONE 7(9):e45475

    Article  PubMed  PubMed Central  Google Scholar 

  3. Masui K, Cloughesy TF, Mischel PS (2012) Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. Neuropathol Appl Neurobiol 38(3):271–291

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. 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 352:987–996

    Article  PubMed  CAS  Google Scholar 

  5. Goode EL, Ulrich CM, Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomark Prev 11(12):1513–1530

    CAS  Google Scholar 

  6. Vodicka P, Kumar R, Stetina R, Sanyal S, Soucek P, Haufroid V, Dusinska M, Kuricova M, Zamecnikova M, Musak L, Buchancova J, Norppa H, Hirvonen A, Vodickova L, Naccarati A, Matousu Z, Hemminki K (2004) Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 25(5):757–763

    Article  PubMed  CAS  Google Scholar 

  7. Wang Y, Spitz MR, Zhu Y, Dong Q, Shete S, Wu X (2003) From genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair (Amst) 2(8):901–908

    Article  CAS  Google Scholar 

  8. Alsbeih G, El-Sebaie M, Al-Harbi N, Al-Buhairi M, Al-Hadyan K, Al-Rajhi N (2007) Radiosensitivity of human fibroblasts is associated with amino acid substitution variants in susceptible genes and correlates with the number of risk alleles. Int J Radiat Oncol Biol Phys 68(1):229–235

    Article  PubMed  CAS  Google Scholar 

  9. Bishay K, Ory K, Olivier MF, Lebeau J, Levalois C, Chevillard S (2001) DNA damage-related RNA expression to assess individual sensitivity to ionizing radiation. Carcinogenesis 22(8):1179–1183

    Article  PubMed  CAS  Google Scholar 

  10. Saydam O, Saydam N, Glauser DL, Pruschy M, Dinh-Van V, Hilbe M, Jacobs AH, Ackermann M, Fraefel C (2007) HSV-1 amplicon-mediated post-transcriptional inhibition of Rad51 sensitizes human glioma cells to ionizing radiation. Gene Ther 14(15):1143–1151

    Article  PubMed  CAS  Google Scholar 

  11. Cheng D, Shi H, Zhang K, Yi L, Zhen G (2014) RAD51 Gene 135G/C polymorphism and the risk of four types of common cancers: a meta-analysis. Diagn Pathol 9:18

    Article  PubMed  PubMed Central  Google Scholar 

  12. Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA (2012) An integrated map of genetic variation from 1092 human genomes. Nature 491(7422):56–65

    Article  Google Scholar 

  13. Michalska MM, Samulak D, Romanowicz H, Smolarz B (2014) Association of polymorphisms in the 5′ untranslated region of RAD51 gene with risk of endometrial cancer in the Polish population. Arch Gynecol Obstet 290(5):985–991

    Article  PubMed  PubMed Central  Google Scholar 

  14. Raderschall E, Stout K, Freier S, Suckow V, Schweiger S, Haaf T (2002) Elevated levels of Rad51 recombination protein in tumor cells. Cancer Res 62:219–225

    PubMed  CAS  Google Scholar 

  15. Flygare J, Fält S, Ottervald J, Castro J, Dackland A-L, Hellgren D, Wennborg A (2001) Effects of HsRad51 overexpression on cell proliferation, cell cycle progression, and apoptosis. Exp Cell Res 268:61–69

    Article  PubMed  CAS  Google Scholar 

  16. Zhao M, Chen P, Dong Y, Zhu X, Zhang X (2014) Relationship between Rad51 G135C and G172T variants and the susceptibility to cancer: a meta-analysis involving 54 case-control studies. PLoS ONE 9(1):e87259

    Article  PubMed  PubMed Central  Google Scholar 

  17. Thacker J (2005) The RAD51 gene family, genetic instability and cancer. Cancer Lett 219(2):125–135

    Article  PubMed  CAS  Google Scholar 

  18. Wang LE, Bondy ML, Shen H, El-Zein R, Aldape K, Cao Y, Pudavalli V, Levin VA, Yung WK, Wei Q (2004) Polymorphisms of DNA repair genes and risk of glioma. Cancer Res 64(16):5560–5563

    Article  PubMed  CAS  Google Scholar 

  19. Hasselbach L, Haase S, Fischer D, Kolberg HC, Stürzbecher HW (2005) Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur J Gynaecol Oncol 26(6):589–599

    PubMed  CAS  Google Scholar 

  20. Zhao M, Chen P, Dong Y, Zhu X, Zhang X (2014) Relationship between Rad51 G135C and G172T variants and the susceptibility to cancer: a meta-analysis involving 54 case-control studies. PLoS ONE 9(1):e87259

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Surgical, Molecular and Ultrastructural Pathology, University Hospital of Pisa, Via Roma 57, 56126, Pisa, PI, Italy

    S. Franceschi, K. Zavaglia, G. Bevilacqua & A. G. Naccarato

  2. Pisa Science Foundation, Via Panfilo Castaldi 2, 56121, Pisa, PI, Italy

    S. Franceschi, C. M. Mazzanti, F. Lessi, P. Aretini, M. La Ferla & V. De Gregorio

  3. Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar

    S. Tomei

  4. Radiotherapy Unit, University Hospital of Pisa, Via Roma 67, 56126, Pisa, PI, Italy

    F. Pasqualetti

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  1. S. Franceschi
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  2. S. Tomei
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  3. C. M. Mazzanti
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  4. F. Lessi
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  6. M. La Ferla
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  7. V. De Gregorio
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  8. F. Pasqualetti
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  9. K. Zavaglia
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  10. G. Bevilacqua
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  11. A. G. Naccarato
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Correspondence to S. Franceschi.

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The authors declare that there are no conflicts of interest.

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

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Table S1

SNPs genotyping analysis. Gene name; exon, position and codon (when translated) of the SNP; molecular substitutions (base and AA when translated); reference SNP ID number. (DOCX 13 kb)

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Franceschi, S., Tomei, S., Mazzanti, C.M. et al. Association between RAD 51 rs1801320 and susceptibility to glioblastoma. J Neurooncol 126, 265–270 (2016). https://doi.org/10.1007/s11060-015-1974-z

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  • DOI: https://doi.org/10.1007/s11060-015-1974-z

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