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Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis

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Tumor Biology

A Commentary to this article was published on 23 December 2015

Abstract

Polymorphisms in interleukin (IL)-4/IL-13 pathway genes have previously been reported to be associated with glioma susceptibility, although results are inconsistent. We therefore performed an updated meta-analysis to determine a more precise estimation of this relationship. Twelve eligible studies were identified by searching PubMed, EMBASE, Web of Science, and the Cochrane Library electronic databases. Nine polymorphisms in genes within the IL-4/IL-13 pathway (IL-4 rs2243250, rs2070874, rs2243248, IL-4R rs1805011, rs1805012, rs1805015, rs1801275, and IL-13 rs20541 and rs1800925) were assessed for their relationship with glioma risk by computing odds ratios (ORs) and corresponding 95 % confidence intervals (CIs). Akaike’s information criterion (AIC) was used to identify the best genetic model for each polymorphism. No association between IL-4/IL-13 pathway genetic polymorphisms and glioma risk was observed in the overall population, although a significant association was found between rs2234248 and glioblastoma when stratified by histological subtype (log-additive model, OR 1.57, 95 % CI 1.11–2.24). This meta-analysis therefore suggested that IL-4/IL-13 pathway genetic polymorphisms are not associated with glioma risk.

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References

  1. Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol. 2005;109(1):93–108. doi:10.1007/s00401-005-0991-y.

    Article  PubMed  Google Scholar 

  2. Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol. 2006;2(9):494–503. doi:10.1038/ncpneuro0289. quiz 1 p following 16.

    Article  PubMed  Google Scholar 

  3. Schoemaker MJ, Swerdlow AJ, Hepworth SJ, McKinney PA, van Tongeren M, Muir KR. History of allergies and risk of glioma in adults. Int J Cancer. 2006;119(9):2165–72. doi:10.1002/ijc.22091.

    Article  CAS  PubMed  Google Scholar 

  4. Wigertz A, Lonn S, Schwartzbaum J, Hall P, Auvinen A, Christensen HC, et al. Allergic conditions and brain tumor risk. Am J Epidemiol. 2007;166(8):941–50. doi:10.1093/aje/kwm203.

    Article  PubMed  Google Scholar 

  5. Linos E, Raine T, Alonso A, Michaud D. Atopy and risk of brain tumors: a meta-analysis. J Natl Cancer Inst. 2007;99(20):1544–50. doi:10.1093/jnci/djm170.

    Article  PubMed  Google Scholar 

  6. Chen C, Xu T, Chen J, Zhou J, Yan Y, Lu Y, et al. Allergy and risk of glioma: a meta-analysis. Eur J Neurol. 2011;18(3):387–95. doi:10.1111/j.1468-1331.2010.03187.x.

    Article  CAS  PubMed  Google Scholar 

  7. Calboli FC, Cox DG, Buring JE, Gaziano JM, Ma J, Stampfer M, et al. Prediagnostic plasma IgE levels and risk of adult glioma in four prospective cohort studies. J Natl Cancer Inst. 2011;103(21):1588–95. doi:10.1093/jnci/djr361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schlehofer B, Siegmund B, Linseisen J, Schuz J, Rohrmann S, Becker S, et al. Primary brain tumours and specific serum immunoglobulin E: a case–control study nested in the European Prospective Investigation into Cancer and Nutrition cohort. Allergy. 2011;66(11):1434–41. doi:10.1111/j.1398-9995.2011.02670.x.

    Article  CAS  PubMed  Google Scholar 

  9. Akdis M. Healthy immune response to allergens: T regulatory cells and more. Curr Opin Immunol. 2006;18(6):738–44. doi:10.1016/j.coi.2006.06.003.

    Article  CAS  PubMed  Google Scholar 

  10. de Vries JE. The role of IL-13 and its receptor in allergy and inflammatory responses. J Allergy Clin Immunol. 1998;102(2):165–9. doi:10.1016/S0091-6749(98)70080-6.

    Article  PubMed  Google Scholar 

  11. Barna BP, Estes ML, Pettay J, Iwasaki K, Zhou P, Barnett GH. Human astrocyte growth regulation: interleukin-4 sensitivity and receptor expression. J Neuroimmunol. 1995;60(1–2):75–81. doi:10.1016/0165-5728(95)00055-7.

    Article  CAS  PubMed  Google Scholar 

  12. Liu H, Jacobs BS, Liu J, Prayson RA, Estes ML, Barnett GH, et al. Interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: non-neoplastic glia and low-grade astrocytoma differ from malignant glioma. Cancer Immunol Immunother. 2000;49(6):319–24. doi:10.1007/s002620000110.

    Article  CAS  PubMed  Google Scholar 

  13. Loza MJ, Chang BL. Association between Q551R IL4R genetic variants and atopic asthma risk demonstrated by meta-analysis. J Allergy Clin Immunol. 2007;120(3):578–85. doi:10.1016/j.jaci.2007.05.019.

    Article  CAS  PubMed  Google Scholar 

  14. Cui L, Jia J, Ma CF, Li SY, Wang YP, Guo XM, et al. IL-13 polymorphisms contribute to the risk of asthma: a meta-analysis. Clin Biochem. 2012;45(4–5):285–8. doi:10.1016/j.clinbiochem.2011.12.012.

    Article  CAS  PubMed  Google Scholar 

  15. Schwartzbaum J, Ahlbom A, Malmer B, Lonn S, Brookes AJ, Doss H, et al. Polymorphisms associated with asthma are inversely related to glioblastoma multiforme. Cancer Res. 2005;65(14):6459–65. doi:10.1158/0008-5472.CAN-04-3728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wiemels JL, Wiencke JK, Kelsey KT, Moghadassi M, Rice T, Urayama KY, et al. Allergy-related polymorphisms influence glioma status and serum IgE levels. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1229–35. doi:10.1158/1055-9965.EPI-07-0041.

    Article  CAS  PubMed  Google Scholar 

  17. Schwartzbaum JA, Ahlbom A, Lonn S, Malmer B, Wigertz A, Auvinen A, et al. An international case–control study of interleukin-4Ralpha, interleukin-13, and cyclooxygenase-2 polymorphisms and glioblastoma risk. Cancer Epidemiol Biomarkers Prev. 2007;16(11):2448–54. doi:10.1158/1055-9965.EPI-07-0480.

    Article  CAS  PubMed  Google Scholar 

  18. Guo J, Shi L, Li M, Xu J, Yan S, Zhang C, et al. Association of the interleukin-4Ralpha rs1801275 and rs1805015 polymorphisms with glioma risk. Tumour Biol. 2013. doi:10.1007/s13277-013-1080-9.

    PubMed Central  Google Scholar 

  19. Sun G, Wang X, Shi L, Yue X, Fu L, Chen C, et al. Association between polymorphisms in interleukin-4Ralpha and interleukin-13 and glioma risk: a meta-analysis. Cancer Epidemiol. 2013;37(3):306–10. doi:10.1016/j.canep.2013.01.003.

    Article  CAS  PubMed  Google Scholar 

  20. 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  CAS  PubMed  Google Scholar 

  21. Amirian E, Liu Y, Scheurer ME, El-Zein R, Gilbert MR, Bondy ML. Genetic variants in inflammation pathway genes and asthma in glioma susceptibility. Neuro Oncol. 2010;12(5):444–52. doi:10.1093/neuonc/nop057.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Walsh KM, Anderson E, Hansen HM, Decker PA, Kosel ML, Kollmeyer T, et al. Analysis of 60 reported glioma risk SNPs replicates published GWAS findings but fails to replicate associations from published candidate-gene studies. Genet Epidemiol. 2013;37(2):222–8. doi:10.1002/gepi.21707.

    Article  PubMed  Google Scholar 

  23. Backes DM, Siddiq A, Cox DG, Calboli FC, Gaziano JM, Ma J, et al. Single-nucleotide polymorphisms of allergy-related genes and risk of adult glioma. J Neurooncol. 2013;113(2):229–38. doi:10.1007/s11060-013-1122-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Al-Moundhri MS, Al-Nabhani M, Al-Bahrani B, Burney IA, Al-Madhani A, Ganguly SS, et al. Interleukin-1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms and gastric cancer risk in an Omani Arab population. Gastric Cancer. 2006;9(4):284–90. doi:10.1007/s10120-006-0392-5.

    Article  CAS  PubMed  Google Scholar 

  25. Gao LB, Pan XM, Li LJ, Liang WB, Zhu Y, Zhang LS, et al. RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies. Breast Cancer Res Treat. 2011;125(3):827–35. doi:10.1007/s10549-010-0995-8.

    Article  CAS  PubMed  Google Scholar 

  26. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58. doi:10.1002/sim.1186.

    Article  PubMed  Google Scholar 

  27. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88. doi:10.1016/0197-2456(86)90046-2.

    Article  CAS  PubMed  Google Scholar 

  28. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48. doi:10.1093/jnci/22.4.719.

    CAS  PubMed  Google Scholar 

  29. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295(6):676–80. doi:10.1001/jama.295.6.676.

    Article  CAS  PubMed  Google Scholar 

  30. 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  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sanson M, Hosking FJ, Shete S, Zelenika D, Dobbins SE, Ma Y, et al. Chromosome 7p11.2 (EGFR) variation influences glioma risk. Hum Mol Genet. 2011;20(14):2897–904. doi:10.1093/hmg/ddr192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Walsh KM, Codd V, Smirnov IV, Rice T, Decker PA, Hansen HM, et al. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nat Genet. 2014;46(7):731–5. doi:10.1038/ng.3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li W, Qian X, Teng H, Ding Y, Zhang L. Association of interleukin-4 genetic polymorphisms with sporadic Alzheimer’s disease in Chinese Han population. Neurosci Lett. 2014;563:17–21. doi:10.1016/j.neulet.2014.01.019.

    Article  CAS  PubMed  Google Scholar 

  35. Cinek O, Vavrincova P, Striz I, Drevinek P, Sedlakova P, Vavrinec J, et al. Association of single nucleotide polymorphisms within cytokine genes with juvenile idiopathic arthritis in the Czech population. J Rheumatol. 2004;31(6):1206–10.

    CAS  PubMed  Google Scholar 

  36. Schwartzbaum J, Jonsson F, Ahlbom A, Preston-Martin S, Lonn S, Soderberg KC, et al. Cohort studies of association between self-reported allergic conditions, immune-related diagnoses and glioma and meningioma risk. Int J Cancer. 2003;106(3):423–8. doi:10.1002/ijc.11230.

    Article  CAS  PubMed  Google Scholar 

  37. Schlehofer B, Blettner M, Preston-Martin S, Niehoff D, Wahrendorf J, Arslan A, et al. Role of medical history in brain tumour development. Results from the international adult brain tumour study. Int J Cancer. 1999;82(2):155–60. doi:10.1002/(SICI)1097-0215(19990719)82:2<155::AID-IJC1>3.0.CO;2-P.

    Article  CAS  PubMed  Google Scholar 

  38. Maier LM, Howson JM, Walker N, Spickett GP, Jones RW, Ring SM, et al. Association of IL13 with total IgE: evidence against an inverse association of atopy and diabetes. J Allergy Clin Immunol. 2006;117(6):1306–13. doi:10.1016/j.jaci.2005.12.1354.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Melissa L. Bondy from the Texas MD Anderson Cancer Center and Dr. Kyle M. Walsh from the Helen Diller Family Comprehensive Cancer Center for generously providing their data.

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Authors and Affiliations

  1. Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Peiqin Chen, Kun Chen, Tao Xu & Chun Luo

  2. Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Chao Chen

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  1. Peiqin Chen
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Correspondence to Chun Luo.

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Peiqin Chen and Chao Chen contributed equally to this work.

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Meta-analysis for the association between IL-4/IL-13 pathway genetic polymorphisms and glioblastoma risk (GIF 122 kb)

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Chen, P., Chen, C., Chen, K. et al. Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis. Tumor Biol. 36, 121–127 (2015). https://doi.org/10.1007/s13277-014-2895-8

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  • DOI: https://doi.org/10.1007/s13277-014-2895-8

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