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RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population

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Tumor Biology

Abstract

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case–control study from Xi’an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

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References

  1. Nakamura M, Shimada K, Ishida E, Higuchi T, Nakase H, Sakaki T, et al. Molecular pathogenesis of pediatric astrocytic tumors. Neuro Oncol. 2007;9(2):113–23. doi:10.1215/15228517-2006-036.

    Article  PubMed  CAS  Google Scholar 

  2. Foong CS, Sandanaraj E, Brooks HB, Campbell RM, Ang BT, Chong YK et al. Glioma-propagating cells as an in vitro screening platform: PLK1 as a case study. J Biomol Screen. 2012. doi:10.1177/1087057112457820.

  3. Malmer B, Gronberg H, Bergenheim AT, Lenner P, Henriksson R. Familial aggregation of astrocytoma in northern Sweden: an epidemiological cohort study. Int J Cancer. 1999;81(3):366–70. doi:10.1002/(SICI)1097-0215(19990505)81:3<366::AID-IJC9>3.0.CO;2-0.

    Article  PubMed  CAS  Google Scholar 

  4. Wiemels JL, Wiencke JK, Patoka J, Moghadassi M, Chew T, McMillan A, et al. Reduced immunoglobulin E and allergy among adults with glioma compared with controls. Cancer Res. 2004;64(22):8468–73. doi:10.1158/0008-5472.CAN-04-1706.

    Article  PubMed  CAS  Google Scholar 

  5. Liu Y, Shete S, Hosking F, Robertson L, Houlston R, Bondy M. Genetic advances in glioma: susceptibility genes and networks. Curr Opin Genet Dev. 2010;20(3):239–44. doi:10.1016/j.gde.2010.02.001.

    Article  PubMed  CAS  Google Scholar 

  6. Rajaraman P, Wang SS, Rothman N, Brown MM, Black PM, Fine HA, et al. Polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults. Cancer Epidemiol Biomarkers Prev. 2007;16(8):1655–61. doi:10.1158/1055-9965.EPI-07-0314.

    Article  PubMed  CAS  Google Scholar 

  7. Bethke L, Webb E, Murray A, Schoemaker M, Johansen C, Christensen HC, et al. Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma. Hum Mol Genet. 2008;17(6):800–5. doi:10.1093/hmg/ddm351.

    Article  PubMed  CAS  Google Scholar 

  8. Lai R, Crevier L, Thabane L. Genetic polymorphisms of glutathione S-transferases and the risk of adult brain tumors: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2005;14(7):1784–90. doi:10.1158/1055-9965.EPI-05-0105.

    Article  PubMed  CAS  Google Scholar 

  9. Liu Y, Zhang H, Zhou K, Chen L, Xu Z, Zhong Y, et al. Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma. Carcinogenesis. 2007;28(9):1906–13. doi:10.1093/carcin/bgm073.

    Article  PubMed  CAS  Google Scholar 

  10. Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009;41(8):899–904. doi:10.1038/ng.407.

    Article  PubMed  CAS  Google Scholar 

  11. Andersson U, Schwartzbaum J, Wiklund F, Sjostrom S, Liu Y, Tsavachidis S, et al. A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk. Acta Oncol. 2010;49(6):767–75. doi:10.3109/0284186X.2010.480980.

    Article  PubMed  CAS  Google Scholar 

  12. Brenner AV, Butler MA, Wang SS, Ruder AM, Rothman N, Schulte PA, et al. Single-nucleotide polymorphisms in selected cytokine genes and risk of adult glioma. Carcinogenesis. 2007;28(12):2543–7. doi:10.1093/carcin/bgm210.

    Article  PubMed  CAS  Google Scholar 

  13. Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, et al. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009;41(8):905–8. doi:10.1038/ng.408.

    Article  PubMed  CAS  Google Scholar 

  14. Gabriel S, Ziaugra L, Tabbaa D. SNP genotyping using the Sequenom MassARRAY iPLEX platform. Curr Protoc Hum Genet. 2009;Chapter 2:Unit 2 12. doi:10.1002/0471142905.hg0212s60.

  15. Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007;39(3):347–51. doi:10.1038/ng1975.

    Article  PubMed  CAS  Google Scholar 

  16. Adamec C. Example of the use of the nonparametric test. Test X2 for comparison of 2 independent examples. Cesk Zdrav. 1964;12:613–9.

    PubMed  CAS  Google Scholar 

  17. Bland JM, Altman DG. Statistics notes. The odds ratio. BMJ. 2000;320(7247):1468.

    Article  PubMed  CAS  Google Scholar 

  18. Youds JL, Mets DG, McIlwraith MJ, Martin JS, Ward JD, ONeil NJ, et al. RTEL-1 enforces meiotic crossover interference and homeostasis. Science. 2010;327(5970):1254–8. doi:10.1126/science.1183112.

    Article  PubMed  CAS  Google Scholar 

  19. Uringa EJ, Lisaingo K, Pickett HA, Brind'amour J, Rohde JH, Zelensky A, et al. RTEL1 contributes to DNA replication and repair and telomere maintenance. Mol Biol Cell. 2012;23(14):2782–92. doi:10.1091/mbc.E12-03-0179.

    Article  PubMed  CAS  Google Scholar 

  20. Vannier JB, Pavicic-Kaltenbrunner V, Petalcorin MI, Ding H, Boulton SJ. RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell. 2012;149(4):795–806. doi:10.1016/j.cell.2012.03.030.

    Article  PubMed  CAS  Google Scholar 

  21. Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ, Petalcorin MI, et al. RTEL1 maintains genomic stability by suppressing homologous recombination. Cell. 2008;135(2):261–71. doi:10.1016/j.cell.2008.08.016.

    Article  PubMed  CAS  Google Scholar 

  22. Wu X, Sandhu S, Nabi Z, Ding H. Generation of a mouse model for studying the role of upregulated RTEL1 activity in tumorigenesis. Transgenic Res. 2012. doi:10.1007/s11248-011-9586-7.

  23. Bai C, Connolly B, Metzker ML, Hilliard CA, Liu X, Sandig V, et al. Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster. Proc Natl Acad Sci U S A. 2000;97(3):1230–5.

    Article  PubMed  CAS  Google Scholar 

  24. Muleris M, Almeida A, Gerbault-Seureau M, Malfoy B, Dutrillaux B. Identification of amplified DNA sequences in breast cancer and their organization within homogeneously staining regions. Genes Chromosomes Cancer. 1995;14(3):155–63.

    Article  PubMed  CAS  Google Scholar 

  25. Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 1998;396(6712):699–703. doi:10.1038/25387.

    Article  PubMed  CAS  Google Scholar 

  26. Song X, Zhou K, Zhao Y, Huai C, Yu H, Chen Y, et al. Fine mapping analysis of a region of 20q13.33 identified five independent susceptibility loci for glioma in a Chinese Han population. Carcinogenesis. 2012;33(5):1065–71.

    Article  PubMed  CAS  Google Scholar 

  27. Wang SS, Hartge P, Yeager M, Carreon T, Ruder AM, Linet M, et al. Joint associations between genetic variants and reproductive factors in glioma risk among women. Am J Epidemiol. 2011;174(8):901–8. doi:10.1093/aje/kwr184.

    Article  PubMed  Google Scholar 

  28. Garrels W, Kues WA, Herrmann D, Holler S, Baulain U, Niemann H. Ectopic expression of human telomerase RNA component results in increased telomerase activity and elongated telomeres in bovine blastocysts. Biol Reprod. 2012. doi:10.1095/biolreprod.112.100198.

    PubMed  Google Scholar 

  29. Cudre-Mauroux C, Occhiodoro T, Konig S, Salmon P, Bernheim L, Trono D. Lentivector-mediated transfer of Bmi-1 and telomerase in muscle satellite cells yields a duchenne myoblast cell line with long-term genotypic and phenotypic stability. Hum Gene Ther. 2003;14(16):1525–33. doi:10.1089/104303403322495034.

    Article  PubMed  CAS  Google Scholar 

  30. Di Donna S, Renault V, Forestier C, Piron-Hamelin G, Thiesson D, Cooper RN, et al. Regenerative capacity of human satellite cells: the mitotic clock in cell transplantation. Neurol Sci. 2000;21(5):S943–51.

    Article  PubMed  Google Scholar 

  31. Seigneurin-Venin S, Bernard V, Moisset PA, Ouellette MM, Mouly V, Di Donna S, et al. Transplantation of normal and DMD myoblasts expressing the telomerase gene in SCID mice. Biochem Biophys Res Commun. 2000;272(2):362–9. doi:10.1006/bbrc.2000.2735.

    Article  PubMed  CAS  Google Scholar 

  32. Seigneurin-Venin S, Bernard V, Tremblay JP. Telomerase allows the immortalization of T antigen-positive DMD myoblasts: a new source of cells for gene transfer application. Gene Ther. 2000;7(7):619–23. doi:10.1038/sj.gt.3301132.

    Article  PubMed  CAS  Google Scholar 

  33. Li G, Jin TB, Wei XB, He SM, Liang HJ, Yang HX, et al. Selected polymorphisms of GSTP1 and TERT were associated with glioma risk in Han Chinese. Cancer Epidemiol. 2012;36(6):525–7. doi:10.1016/j.canep.2012.06.008.

    Article  PubMed  Google Scholar 

  34. Melin B. Genetic causes of glioma: new leads in the labyrinth. Curr Opin Oncol. 2011;23(6):643–7. doi:10.1097/CCO.0b013e32834a6f61.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work is supported by the National Natural Science Foundation of China (no. 81272776) and China Postdoctoral Science Foundation Project (no. 2013T60886).

Conflicts of interest

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Authors and Affiliations

  1. School of Life Sciences, Northwest University, Xi’an, 710069, China

    Tian-Bo Jin, Jia-Yi Zhang & Chao Chen

  2. National Engineering Research Center for Miniaturized Detection Systems, Xi’an, 710069, China

    Tian-Bo Jin, Jia-Yi Zhang, Shu-Li Du, Ting-Ting Geng, Jing Gao, Qian-Ping Liu & Chao Chen

  3. Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Tibet University for Nationalities, Xianyang, Shaanxi, 712082, China

    Tian-Bo Jin & Long-Li Kang

  4. Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, 710038, China

    Gang Li & Guo-Dong Gao

  5. Medical Center of Tangdu Hospital, The Fourth Military Medical University, Xi’an, 710038, China

    Shan-Qu Li

  6. Mailbox 386, #229 North Taibai Road, Xi’an, 710069, Shaanxi, China

    Chao Chen

  7. No. 569 Xinsi Road, Xi’an, 710038, Shaanxi, China

    Shan-Qu Li

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  1. Tian-Bo Jin
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Correspondence to Chao Chen or Shan-Qu Li.

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Tian-Bo Jin and Jia-Yi Zhang are joint first authors.

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Jin, TB., Zhang, JY., Li, G. et al. RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population. Tumor Biol. 34, 3659–3666 (2013). https://doi.org/10.1007/s13277-013-0947-0

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  • DOI: https://doi.org/10.1007/s13277-013-0947-0

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