The XRCC3 Thr241Met Polymorphism Influences Glioma Risk - A Meta-analysis

  • Jiang, Jun (Radiation Oncology, The First Affiliated Hospital of Anhui Medical University) ;
  • Quan, Xun-Feng (Radiation Oncology, The First Affiliated Hospital of Anhui Medical University) ;
  • Zhang, Li (Radiation Oncology, The First Affiliated Hospital of Anhui Medical University) ;
  • Wang, Yi-Chun (Radiation Oncology, The First Affiliated Hospital of Anhui Medical University)
  • Published : 2013.05.30


Background: Findings from previous published studies regarding the association of the XRCC3 Thr241Met polymorphism with glioma susceptibility have often been conflicting. Therefore, a meta-analysis including all available publications was carried out to make a more precise estimation of the potential relationship. Methods: By searching the electronic databases of Pubmed and Embase (up to April 1st, 2013), a total of nine case-control studies with 3,752 cases and 4,849 controls could be identified for inclusion in the current meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. Results: This meta-analysis showed the XRCC3 Thr241Met polymorphism to be significantly associated with decreased glioma risk in the allelic model (Met allele vs. Thr allele: OR= 0.708, 95%CI= 0.631-0.795). Moreover, we also observed a statistically significant association between the XRCC3 Thr241Met polymorphism and reduced glioma risk in analyses stratified by ethnicity (Asian) and source of controls (hospital based) in the allelic model. Conclusions: Current evidence suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for glioma development, especially in Asians.


  1. Abdel-Rahman SZ, El-Zein RA (2011). Evaluating the effects of genetic variants of DNA repair genes using cytogenetic mutagen sensitivity approaches. Biomarkers, 16, 393-404.
  2. Begg CB , Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101.
  3. Bondy ML, Scheurer ME, Malmer B, et al (2008). Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium. Cancer, 113, 1953-68.
  4. Custodio AC, Almeida LO, Pinto GR, et al (2012). Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas. Genet Mol Res, 11, 332-9.
  5. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  6. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34.
  7. Griffin CS, Simpson PJ, Wilson CR, et al (2000). Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat Cell Biol, 2, 757-61.
  8. Higgins JP, Thompson SG, Deeks JJ, et al (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557-60.
  9. Jacobs DI, Bracken MB (2012). Association between XRCC1 polymorphism 399 G->A and glioma among Caucasians: a systematic review and meta-analysis. BMC Med Genet., 13, 97.
  10. Jemal A, Siegel R, Ward E, et al (2009). Cancer statistics. CA Cancer J Clin, 59, 225-49.
  11. Kiuru A, Lindholm C, Heinavaara S, et al (2008). XRCC1 and XRCC3 variants and risk of glioma and meningioma. J Neurooncol, 88, 135-42.
  12. Kiyohara C, Takayama K, Nakanishi Y (2006). Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk: a meta-analysis. Lung Cancer, 54, 267-83.
  13. Liu HB, Peng YP, Dou CW, et al (2012). Comprehensive study on associations between nine SNPs and glioma risk. Asian Pac J Cancer Prev, 13, 4905-8.
  14. Liu YH, Scheurer ME, El-Zein R, et al (2009). Association and Interactions between DNA Repair Gene Polymorphisms and Adult Glioma. Epidemiol Biomarkers Prev, 18, 204-14.
  15. Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, et al (2007). Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer, 7, 162.
  16. Louis DN, Ohgaki H, Wiestler OD, et al (2007). The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol, 114, 97-109.
  17. Luo KQ, Mu SQ, Wu ZX, et al (2013). Polymorphisms in DNA repair genes and risk of glioma and meningioma. Asian Pac J Cancer Prev, 14, 449-52.
  18. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  19. Matullo G, Dunning AM, Guarrera S, et al (2006). DNA repair polymorphisms and cancer risk in non- smokers in a cohort study. Carcinogenesis, 27, 997-1007.
  20. Mittal RD, Gangwar R, Mandal RK, et al (2012). Gene variants of XRCC4 and XRCC3 and their association with risk for urothelial bladder cancer. Mol Biol Rep, 39, 1667-75.
  21. 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, 3314-24.
  22. Rajaraman P, Hutchinson A, Wichner S, et al (2010). DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma. Neuro Oncol, 12, 37-48.
  23. Romanowicz-Makowska H, Brys M, Forma E, et al (2012). Single nucleotide polymorphism (SNP) Thr241Met in the XRCC3 gene and breast cancer risk in Polish women. Pol J Pathol, 63, 121-5.
  24. Saadat M, Ansari-Lari M (2009). Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a metaanalysis of the literatures. Breast Cancer Res Treat, 115, 137-44.
  25. Schwartzbaum JA, Fisher JL, Aldape KD, et al (2006). Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol, 2, 494-503 (quiz 491 p following 516).
  26. Shen MR, Jones IM, Mohrenweiser H (1998). Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res, 58, 604-8.
  27. Takanami T, Nakamura J, Kubota Y, et al (2005). The Arg280His polymorphism in X-ray repair cross-complementing gene 1 impairs DNA repair ability. Mutat Res, 582, 135-45.
  28. Wang LE, Bondy ML, Shen HB, et al (2004). Polymorphisms of DNA Repair Genes and Risk of Glioma. Cancer Res, 64, 5560-3.
  29. Zhao Y, Deng X, Wang Z, et al (2012). Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population. Asian Pac J Cancer Prev, 13, 665-9.
  30. Zhou KK, Liu Yh, Zhang HS, et al (2009). XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital-based case-control study. Int J Cancer, 124, 2948-53.

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