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Published in: Journal of Neuro-Oncology 2/2016

01-01-2016 | Laboratory Investigation

Association between RAD 51 rs1801320 and susceptibility to glioblastoma

Authors: S. Franceschi, S. Tomei, C. M. Mazzanti, F. Lessi, P. Aretini, M. La Ferla, V. De Gregorio, F. Pasqualetti, K. Zavaglia, G. Bevilacqua, A. G. Naccarato

Published in: Journal of Neuro-Oncology | Issue 2/2016

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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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Literature
1.
go back to reference 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):97–109PubMedPubMedCentralCrossRef 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):97–109PubMedPubMedCentralCrossRef
2.
go back to reference 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):e45475PubMedPubMedCentralCrossRef 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):e45475PubMedPubMedCentralCrossRef
3.
go back to reference 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):271–291PubMedPubMedCentralCrossRef 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):271–291PubMedPubMedCentralCrossRef
4.
go back to reference 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 352:987–996PubMedCrossRef 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 352:987–996PubMedCrossRef
5.
go back to reference 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 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
6.
go back to reference 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):757–763PubMedCrossRef 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):757–763PubMedCrossRef
7.
go back to reference 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):901–908CrossRef 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):901–908CrossRef
8.
go back to reference 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):229–235PubMedCrossRef 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):229–235PubMedCrossRef
9.
go back to reference 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):1179–1183PubMedCrossRef 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):1179–1183PubMedCrossRef
10.
go back to reference 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):1143–1151PubMedCrossRef 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):1143–1151PubMedCrossRef
11.
go back to reference 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 9:18PubMedPubMedCentralCrossRef 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 9:18PubMedPubMedCentralCrossRef
12.
go back to reference 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):56–65CrossRef 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):56–65CrossRef
13.
go back to reference 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):985–991PubMedPubMedCentralCrossRef 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):985–991PubMedPubMedCentralCrossRef
14.
go back to reference Raderschall E, Stout K, Freier S, Suckow V, Schweiger S, Haaf T (2002) Elevated levels of Rad51 recombination protein in tumor cells. Cancer Res 62:219–225PubMed Raderschall E, Stout K, Freier S, Suckow V, Schweiger S, Haaf T (2002) Elevated levels of Rad51 recombination protein in tumor cells. Cancer Res 62:219–225PubMed
15.
go back to reference 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 268:61–69PubMedCrossRef 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 268:61–69PubMedCrossRef
16.
go back to reference 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):e87259PubMedPubMedCentralCrossRef 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):e87259PubMedPubMedCentralCrossRef
17.
go back to reference Thacker J (2005) The RAD51 gene family, genetic instability and cancer. Cancer Lett 219(2):125–135PubMedCrossRef Thacker J (2005) The RAD51 gene family, genetic instability and cancer. Cancer Lett 219(2):125–135PubMedCrossRef
18.
go back to reference 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):5560–5563PubMedCrossRef 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):5560–5563PubMedCrossRef
19.
go back to reference 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):589–599PubMed 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):589–599PubMed
20.
go back to reference 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):e87259PubMedPubMedCentralCrossRef 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):e87259PubMedPubMedCentralCrossRef
Metadata
Title
Association between RAD 51 rs1801320 and susceptibility to glioblastoma
Authors
S. Franceschi
S. Tomei
C. M. Mazzanti
F. Lessi
P. Aretini
M. La Ferla
V. De Gregorio
F. Pasqualetti
K. Zavaglia
G. Bevilacqua
A. G. Naccarato
Publication date
01-01-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1974-z

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