Skip to main content
SpringerLink
Log in

A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Genetic variants found in DNA repair genes (ERCC1, rs3212986; ERCC2, rs13181; ERCC4, rs1800067; ERCC5, rs17655; XRCC1, rs1799782, rs25487, rs25489; XRCC3, rs861539) have been reported to have an ambivalent association with the development of glioma. In the present study, a meta-analysis was conducted to confirm the relationship, taking heterogeneity of population into consideration. We analyzed 21 articles of 6 genes along with 8 single nucleotide polymorphisms (SNPs) (24,078 cases and 30,926 healthy individuals), which assessed the relationship between nucleotide excision, base excision, double-strand break repair gene, and the development of glioma under five models. All statistical analysis was implemented by the software of R 3.2.1, and the relationships between key polymorphic loci in DNA repair genes and glioma were quantified by the pooled odds ratio (OR) and 95 % confidential intervals. Overall, the synthesized evidence demonstrated that the SNP of rs13181 and rs1799782 significantly increased the risk of glioma whereas SNP of rs1800067 were significantly associated with a decrease in the risk of glioma. Additionally, subgroup analyses of 8 SNPs by ethnicity indicated that the mutation of rs13181, rs1800067 were apparently protective factors of glioma among Asians, while the mutation of rs13181 was a risk factors of glioma in Caucasians. Furthermore, the mutation of rs1799782 significantly raises the risk of glioma for Asian. Our study suggested that rs13181*C and rs1799782*A are risk alleles for glioma; rs1800067*A are beneficial alleles for decreased susceptibility to glioma. Future studies with large sample size and other races are strongly recommended to confirm the results from this study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

SNP:

Single nucleotide polymorphism

BER:

Base excision repair

NER:

Nucleotide excision repair

MMR:

Mismatch repair

DSBR:

Double-strand break repair

XRCC :

X-ray cross-complementing group

ERCC1 :

Excision repair cross-complementing group 1

NOS:

Newcastle-Ottawa Scale

References

  1. Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY (2012) Primary brain tumours in adults. Lancet 379(9830):1984–96. doi:10.1016/S0140-6736(11)61346-9

    Article  PubMed  Google Scholar 

  2. Rousseau A, Mokhtari K, Duyckaerts C (2008) The 2007 WHO classification of tumors of the central nervous system—what has changed? Curr Opin Neurol 21(6):720–7. doi:10.1097/WCO.0b013e328312c3a7

    Article  PubMed  Google Scholar 

  3. Chen J, McKay RM, Parada LF (2012) Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell 149(1):36–47. doi:10.1016/j.cell.2012.03.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507. doi:10.1056/NEJMra0708126

    Article  CAS  PubMed  Google Scholar 

  6. Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M (2006) Epidemiology and molecular pathology of glioma. Nat clin pract Neurol 2(9):494–503. doi:10.1038/ncpneuro0289, quiz 491 p following 516

    Article  PubMed  Google Scholar 

  7. Prasad G, Haas-Kogan DA (2009) Radiation-induced gliomas. Expert Rev Neurother 9(10):1511–7. doi:10.1002/pmic.200800802

    Article  CAS  PubMed  Google Scholar 

  8. Bondy M, Wiencke J, Wrensch M, Kyritsis AP (1994) Genetics of primary brain tumors: a review. J Neurooncol 18(1):69–81

    Article  CAS  PubMed  Google Scholar 

  9. Little MP, de Vathaire F, Shamsaldin A, Oberlin O, Campbell S, Grimaud E, Chavaudra J, Haylock RG et al (1998) Risks of brain tumour following treatment for cancer in childhood: modification by genetic factors, radiotherapy and chemotherapy. International journal of cancer Journal international du cancer 78(3):269–75. doi:10.1002/(SICI)1097-0215(19981029)78:3<269::AID-IJC1>3.0.CO;2-T

    Article  CAS  PubMed  Google Scholar 

  10. Bondy ML, Wang LE, El-Zein R, de Andrade M, Selvan MS, Bruner JM, Levin VA, Alfred Yung WK et al (2001) Gamma-radiation sensitivity and risk of glioma. J Natl Cancer Inst 93(20):1553–7

    Article  CAS  PubMed  Google Scholar 

  11. Friedberg EC (2003) DNA damage and repair. Nature 421(6921):436–40. doi:10.1038/nature01408

    Article  PubMed  Google Scholar 

  12. Rajaraman P, Hutchinson A, Wichner S, Black PM, Fine HA, Loeffler JS, Selker RG, Shapiro WR et al (2010) DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma. Neuro Oncol 12(1):37–48. doi:10.1093/neuonc/nop012

    Article  CAS  PubMed  Google Scholar 

  13. Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F, Petticrew M, Altman DG (2003) Evaluating non-randomised intervention studies. Health Technol Assess 7(27):1–173, iii-x

    Article  Google Scholar 

  14. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–60. doi:10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  16. Wang LE, Bondy ML, Shen H, El-Zein R, Aldape K, Cao Y, Pudavalli V, Levin VA et al (2004) Polymorphisms of DNA repair genes and risk of glioma. Cancer Res 64(16):5560–3. doi:10.1158/0008-5472.can-03-2181

    Article  CAS  PubMed  Google Scholar 

  17. Wrensch M, Kelsey KT, Liu M, Miike R, Moghadassi M, Sison JD, Aldape K, McMillan A et al (2005) ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro Oncol 7(4):495–507. doi:10.1215/S1152851705000037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Felini MJ, Olshan AF, Schroeder JC, North KE, Carozza SE, Kelsey KT, Liu M, Rice T et al (2007) DNA repair polymorphisms XRCC1 and MGMT and risk of adult gliomas. Neuroepidemiology 29(1–2):55–8. doi:10.1159/000108919

    Article  PubMed  Google Scholar 

  19. Cengiz SL, Acar H, Inan Z, Yavuz S, Baysefer A (2008) Deoxy-ribonucleic acid repair genes XRCC1 and XPD polymorphisms and brain tumor risk. Neurosciences (Riyadh) 13(3):227–32

    Google Scholar 

  20. McKean-Cowdin R, Barnholtz-Sloan J, Inskip PD, Ruder AM, Butler M, Rajaraman P, Razavi P, Patoka J et al (2009) Associations between polymorphisms in DNA repair genes and glioblastoma. Cancer Epidemiol Biomark Prev: a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 18(4):1118–26. doi:10.1158/1055-9965.EPI-08-1078

    Article  CAS  Google Scholar 

  21. Zhou K, Liu Y, Zhang H, Liu H, Fan W, Zhong Y, Xu Z, Jin L et al (2009) XRCC3 haplotypes and risk of gliomas in a Chinese population: a hospital-based case–control study. Int J Cancer 124(12):2948–53. doi:10.1002/ijc.24307, 2009/03/31 edn

    Article  CAS  PubMed  Google Scholar 

  22. Yosunkaya E, Kucukyuruk B, Onaran I, Gurel CB, Uzan M, Kanigur-Sultuybek G (2010) Glioma risk associates with polymorphisms of DNA repair genes, XRCC1 and PARP1. Br J Neurosurg 24(5):561–5. doi:10.3109/02688697.2010.489655

    Article  PubMed  Google Scholar 

  23. Custodio AC, Almeida LO, Pinto GR, Santos MJ, Almeida JR, Clara CA, Rey JA, Casartelli C (2011) Analysis of the polymorphisms XRCC1Arg194Trp and XRCC1Arg399Gln in gliomas. Genet Mol Res: GMR 10(2):1120–9. doi:10.4238/vol10-2gmr1125

    Article  CAS  PubMed  Google Scholar 

  24. Hu XB, Feng Z, Fan YC, Xiong ZY, Huang QW (2011) Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma. Asian Pac J Cancer Prev 12(11):2981–4

    PubMed  Google Scholar 

  25. Zhou L-Q (2011) Polymorphisms of DNA repair gene XRCC1 and risk of glioma: a case–control study in Southern China. Asian Pac J Cancer Prev 12(10):2547–50

    PubMed  Google Scholar 

  26. Chen D-Q, Yao D-X, Zhao H-Y, Yang S-J (2012) DNA repair gene ERCC1 and XPD polymorphisms predict glioma susceptibility and prognosis. Asian Pac J Cancer Prev 13(6):2791–4. doi:10.7314/apjcp.2012.13.6.2791

    Article  PubMed  Google Scholar 

  27. Custodio AC, Almeida LO, Pinto GR, Santos MJ, Almeida JR, Clara CA, Rey JA, Casartelli C (2012) Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas. Genet mol res : GMR 11(1):332–9. doi:10.4238/2012.February.10.4

    Article  CAS  PubMed  Google Scholar 

  28. Liu H-B, Peng Y-P, Dou C-W, Su X-L, Gao N-K, Tian F-M, Bai J (2012) Comprehensive study on associations between nine SNPs and glioma risk. Asian Pac J Cancer Prev 13(10):4905–8. doi:10.7314/apjcp.2012.13.10.4905

    Article  PubMed  Google Scholar 

  29. Wang D, Hu Y, Gong H, Li J, Ren Y, Li G, Liu A (2012) Genetic polymorphisms in the DNA repair gene XRCC1 and susceptibility to glioma in a Han population in northeastern China: a case–control study. Gene 509(2):223–7. doi:10.1016/j.gene.2012.08.023

    Article  CAS  PubMed  Google Scholar 

  30. Pan WR, Li G, Guan JH (2013) Polymorphisms in DNA repair genes and susceptibility to glioma in a Chinese population. Int J Mol Sci 14(2):3314–24. doi:10.3390/ijms14023314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang XF, Liu S, Shao ZK (2013) Effects of polymorphisms in nucleotide excision repair genes on glioma risk in a Chinese population. Gene 529(2):317–20. doi:10.1016/j.gene.2013.07.025

    Article  CAS  PubMed  Google Scholar 

  32. Zhao P, Zou P, Zhao L, Yan W, Kang C, Jiang T, You Y (2013) Genetic polymorphisms of DNA double-strand break repair pathway genes and glioma susceptibility. BMC Cancer 13:234. doi:10.1186/1471-2407-13-234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gao K, Mu SQ, Wu ZX (2014) Investigation of the effects of single-nucleotide polymorphisms in DNA repair genes on the risk of glioma. Genet Mol Res: GMR 13(1):1203–11. doi:10.4238/2014.February.27.5

    Article  CAS  PubMed  Google Scholar 

  34. Li J, Qu Q, Qu J, Luo WM, Wang SY, He YZ, Luo QS, Xu YX et al (2014) Association between XRCC1 polymorphisms and glioma risk among Chinese population. Med Oncol (Northwood, London, England) 31(10):186. doi:10.1007/s12032-014-0186-2

    Article  Google Scholar 

  35. Xu G, Wang M, Xie W, Bai X (2014) DNA repair gene XRCC3 Thr241Met polymorphism and susceptibility to glioma: a case–control study. Oncology letters 8(2):864–8. doi:10.3892/ol.2014.2192

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, Wang SS, Bondy M, Houlston R et al (2012) Genome-wide association study of glioma and meta-analysis. Hum Genet 131(12):1877–88. doi:10.1007/s00439-012-1212-0

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bondy ML, Scheurer ME, Malmer B, Barnholtz-Sloan JS, Davis FG, Il’yasova D, Kruchko C, McCarthy BJ et al (2008) Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium. Cancer 113(7 Suppl):1953–68. doi:10.1002/cncr.23741

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zhang N, Lin LY, Zhu LL, Wu F, Wen H, Pan D, Huang YC, Chen DQ (2012) ERCC1 polymorphisms and risk of adult glioma in a Chinese population: a hospital-based case–control study. Cancer Invest 30(3):199–202. doi:10.3109/07357907.2011.651233

    Article  PubMed  Google Scholar 

  39. Adel Fahmideh M, Schwartzbaum J, Frumento P, Feychting M (2014) Association between DNA repair gene polymorphisms and risk of glioma: a systematic review and meta-analysis. Neuro Oncol 16(6):807–14. doi:10.1093/neuonc/nou003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sung P, Bailly V, Weber C, Thompson LH, Prakash L, Prakash S (1993) Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature 365(6449):852–5. doi:10.1038/365852a0

    Article  CAS  PubMed  Google Scholar 

  41. de Boer J, Hoeijmakers JH (2000) Nucleotide excision repair and human syndromes. Carcinogenesis 21(3):453–60

    Article  PubMed  Google Scholar 

  42. Chen P, Wiencke J, Aldape K, Kesler-Diaz A, Miike R, Kelsey K, Lee M, Liu J et al (2000) Association of an ERCC1 polymorphism with adult-onset glioma. Cancer Epidemiol Biomarkers Prev: a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 9(8):843–7

    CAS  Google Scholar 

  43. Caggana M, Kilgallen J, Conroy JM, Wiencke JK, Kelsey KT, Miike R, Chen P, Wrensch MR (2001) Associations between ERCC2 polymorphisms and gliomas. Cancer Epidemiol Biomarkers Prev: a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 10(4):355–60

    CAS  Google Scholar 

  44. Cui QK, Zhu JX, Liu WD, Wang YH, Wang ZG (2014) Association of ERCC1 rs3212986 & ERCC2 rs13181 polymorphisms with the risk of glioma. Pakistan j med sci 30(6):1409–1414. doi:10.12669/pjms.306.5221

    Google Scholar 

  45. Yuan Q, Liu JW, Xing CZ, Yuan Y (2014) Associations of ERCC4 rs1800067 polymorphism with cancer risk: an updated meta-analysis. Asian Pac J Cancer Prev: APJCP 15(18):7639–44

    Article  PubMed  Google Scholar 

  46. Geng P, Ou J, Li J, Liao Y, Wang N, Xie G, Sa R, Liu C, Xiang L, Liang H (2015) A Comprehensive analysis of influence ERCC polymorphisms confer on the development of brain tumors. Molecular Neurobiology. doi:10.1007/s12035-015-9371-3

  47. Liu HB, Peng YP, Dou CW, Su XL, Gao NK, Tian FM, Bai J (2012) Comprehensive study on associations between nine SNPs and glioma risk. Asian Pac J Cancer Prev 13(10):4905–8

    Article  Google Scholar 

  48. Hanssen-Bauer A, Solvang-Garten K, Akbari M, Otterlei M (2012) X-ray repair cross complementing protein 1 in base excision repair. Int J Mol Sci 13(12):17210–29. doi:10.3390/ijms131217210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lee Y, Katyal S, Li Y, El-Khamisy SF, Russell HR, Caldecott KW, McKinnon PJ (2009) The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1. Nat Neurosci 12(8):973–80. doi:10.1038/nn.2375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhao B, Ye J, Li B, Ma Q, Su G, Han R (2013) DNA repair gene XRCC3 Thr241Met polymorphism and glioma risk: a meta-analysis. International Journal of Clinical and Experimental Medicine 6(6):438–43

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Source of Support

This study was funded by the National Natural Science Foundation of China (no. 81201671 and 81372793) and Foundation of Science and Technology Department of Jilin Province (no. 20140414049GH and 20140101114JC).

Author information

Authors and Affiliations

  1. Department of Pathology, Jilin Medical University, Jilin, 132013, China

    Ling Qi, Dong-hai Zhao, Peng Lv & Wei-yao Wang

  2. Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China

    Hong-quan Yu & Yu Zhang

  3. Department of Radiation Oncology, First Hospital of Jilin University, Changchun, 130021, China

    Li-juan Ding

  4. Medical Research Laboratory, Jilin Medical University, No.5 Jilin District, Jilin, 132013, China

    Ye Xu

Authors
  1. Ling Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong-quan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li-juan Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dong-hai Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peng Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei-yao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ye Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ye Xu.

Ethics declarations

Conflicts of Interest

The authors declared no conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

Forest plot for a ERCC1 rs3212986 and b ERCC5 rs17655 under the allelic model (GIF 29 kb)

High resolution image (EPS 773 kb)

Fig. S2

Forest plot for XRCC1 rs25487 under the allelic model (GIF 23 kb)

High resolution image (EPS 1268 kb)

Fig. S3

Forest plot for a XRCC1 rs25489 and b XRCC3 rs861539 (GIF 37 kb)

High resolution image (EPS 1367 kb)

Fig. S4

Forest plot for cumulative meta-analysis of a rs3212986, b rs13181, c rs1800067, and d rs17655 under the allelic model (GIF 26 kb)

High resolution image (EPS 1413 kb)

Fig. S5

Forest plot for cumulative meta-analysis of a rs1799782, b rs25487, c rs25489, and d rs861539 under the allelic model (GIF 47 kb)

High resolution image (EPS 1593 kb)

Table S1

Sensitivity analysis results of rs1799782, rs25487, rs25489, and rs861539 SNPs (DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qi, L., Yu, Hq., Zhang, Y. et al. A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk. Mol Neurobiol 54, 1314–1325 (2017). https://doi.org/10.1007/s12035-016-9725-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-9725-5

Keywords

Search

Navigation