Tumor Biology

, Volume 34, Issue 2, pp 865–874 | Cite as

No significant association between the XRCC3 Thr241Met polymorphism and lung cancer risk: a meta-analysis

  • Yun-Hua Xu
  • Lin-Ping Gu
  • Ying-Jia Sun
  • Bai-Jun Cheng
  • Shun Lu
Research Article


The development of lung cancer is significantly associated with genetic susceptibility. Findings from previous individual studies regarding the effect of X-ray repair cross-complementing group 3 Thr241Met (XRCC3 Thr241Met) polymorphism on lung cancer risk remained conflicting and inconclusive. Thus, a meta-analysis of previous relevant studies was performed to estimate this effect more precisely and to shed some light on the contradictory findings. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the correlation of XRCC3 Thr241Met polymorphism with lung cancer susceptibility. Stratified analysis according to ethnicity and sensitivity analysis was both conducted for further confirmation. Seventeen independent case–control studies involving 12,610 subjects totally were included into this meta-analysis. Overall, meta-analysis of total included studies showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (ORMet allele vs. Thr allele = 1.01, 95 % CI 0.91–1.13, P OR = 0.810; ORMet/Met vs. Thr/Thr = 1.16, 95 % CI 0.88–1.54, P OR = 0.281; ORThr/Met vs. Thr/Thr = 0.95, 95 % CI 0.86–1.04, P OR = 0.240; ORMet/Met + Thr/Met vs. Thr/Thr = 0.97, 95 % CI 0.89–1.06, P OR = 0.538; ORMet/Met vs. Thr/Thr + Thr/Met = 1.18, 95 % CI 0.91–1.52, P OR = 0.204). Stratified analyses in Asians and Caucasians showed similar results. Sensitivity analysis confirmed the stability and reliability of the findings. This meta-analysis of all available data did not support any appreciable association between the XRCC3 Thr241Met polymorphism and lung cancer risk in any populations.


X-ray repair cross-complementing group 3 Lung cancer Genetic polymorphism Meta-analysis 


Conflicts of interest



  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Steliga MA, Dresler CM. Epidemiology of lung cancer: smoking, secondhand smoke, and genetics. Surg Oncol Clin N Am. 2011;20:605–18.PubMedCrossRefGoogle Scholar
  3. 3.
    McErlean A, Ginsberg MS. Epidemiology of lung cancer. Semin Roentgenol. 2011;46:173–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Brenner DR, McLaughlin JR, Hung RJ. Previous lung diseases and lung cancer risk: a systematic review and meta-analysis. PLoS One. 2011;6:e17479.PubMedCrossRefGoogle Scholar
  5. 5.
    Zhu Y, Spitz MR, Lei L, Mills GB, Wu X. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances lung cancer susceptibility. Cancer Res. 2001;61:7825–9.PubMedGoogle Scholar
  6. 6.
    Kiyohara C, Yoshimasu K, Takayama K, Nakanishi Y. EPHX1 polymorphisms and the risk of lung cancer: a HuGE review. Epidemiology. 2006;17:89–99.PubMedCrossRefGoogle Scholar
  7. 7.
    Hsia TC, Liu CJ, Chu CC, Hang LW, Chang WS, Tsai CW, et al. Association of DNA double-strand break gene XRCC6 genotypes and lung cancer in Taiwan. Anticancer Res. 2012;32:1015–20.PubMedGoogle Scholar
  8. 8.
    David-Beabes GL, Lunn RM, London SJ. No association between the XPD (Lys751G1n) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2001;10:911–2.PubMedGoogle Scholar
  9. 9.
    Improta G, Sgambato A, Bianchino G, Zupa A, Grieco V, La Torre G, et al. Polymorphisms of the DNA repair genes XRCC1 and XRCC3 and risk of lung and colorectal cancer: a case–control study in a Southern Italian population. Anticancer Res. 2008;28:2941–6.PubMedGoogle Scholar
  10. 10.
    Griffin CS, Simpson PJ, Wilson CR, Thacker J. Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat Cell Biol. 2000;2:757–61.PubMedCrossRefGoogle Scholar
  11. 11.
    Matullo G, Guarrera S, Carturan S, Peluso M, Malaveille C, Davico L, et al. DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case–control study. Int J Cancer. 2001;92:562–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Romanowicz-Makowska H, Brys M, Forma E, Maciejczyk R, Polac I, Samulak D, et al. Single nucleotide polymorphism (SNP) Thr241Met in the XRCC3 gene and breast cancer risk in Polish women. Pol J Pathol. 2012;63:121–5.PubMedGoogle Scholar
  13. 13.
    Zhu X, Zhong Z, Zhang X, Zhao X, Xu R, Ren W, et al. DNA repair gene XRCC3 T241M polymorphism and bladder cancer risk in a Chinese population. Genet Test Mol Biomarkers. 2012;16:640–3.PubMedCrossRefGoogle Scholar
  14. 14.
    Jin MJ, Chen K, Song L, Fan CH, Chen Q, Zhu YM, et al. The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population. Cancer Genet Cytogenet. 2005;163:38–43.PubMedCrossRefGoogle Scholar
  15. 15.
    Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet. 1955;19:251–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  17. 17.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRefGoogle Scholar
  18. 18.
    Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.PubMedGoogle Scholar
  19. 19.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCrossRefGoogle Scholar
  21. 21.
    Stuck AE, Rubenstein LZ, Wieland D. Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ. 1998;316:469. author reply 70–1.PubMedCrossRefGoogle Scholar
  22. 22.
    Attia J, Thakkinstian A, D’Este C. Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol. 2003;56:297–303.PubMedCrossRefGoogle Scholar
  23. 23.
    Salanti G, Amountza G, Ntzani EE, Ioannidis JP. Hardy-Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. Eur J Hum Genet. 2005;13:840–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Kiyohara C, Horiuchi T, Takayama K, Nakanishi Y. Genetic polymorphisms involved in carcinogen metabolism and DNA repair and lung cancer risk in a Japanese population. J Thorac Oncol. 2012;7:954–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Huang M, Chen X, Qiu Y, Fan L, Chen J, Cai L. Relationship between XRCC3 gene polymorphisms and lung cancer. Wei Sheng Yan Jiu. 2011;40:187–90 [Article in Chinese].PubMedGoogle Scholar
  26. 26.
    Qian B, Zhang H, Zhang L, Zhou X, Yu H, Chen K. Association of genetic polymorphisms in DNA repair pathway genes with non-small cell lung cancer risk. Lung Cancer. 2011;73:138–46.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang ZL, Zhou CC, Zhang J, Tang L, Su B. Relationship between polymorphisms of DNA repair gene XRCC3 and susceptibility to lung cancer. Zhonghua Jie He He Hu Xi Za Zhi. 2007;30:936–40 [Article in Chinese].PubMedGoogle Scholar
  28. 28.
    Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, Pascual T, Marron MG, Puente XS, et al. Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer. 2007;7:162.PubMedCrossRefGoogle Scholar
  29. 29.
    Matullo G, Dunning AM, Guarrera S, Baynes C, Polidoro S, Garte S, et al. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis. 2006;27:997–1007.PubMedCrossRefGoogle Scholar
  30. 30.
    Zienolddiny S, Campa D, Lind H, Ryberg D, Skaug V, Stangeland L, et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2006;27:560–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Popanda O, Schattenberg T, Phong CT, Butkiewicz D, Risch A, Edler L, et al. Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis. 2004;25:2433–41.PubMedCrossRefGoogle Scholar
  32. 32.
    Jacobsen NR, Raaschou-Nielsen O, Nexo B, Wallin H, Overvad K, Tjonneland A, et al. XRCC3 polymorphisms and risk of lung cancer. Cancer Lett. 2004;213:67–72.PubMedCrossRefGoogle Scholar
  33. 33.
    Harms C, Salama SA, Sierra-Torres CH, Cajas-Salazar N, Au WW. Polymorphisms in DNA repair genes, chromosome aberrations, and lung cancer. Environ Mol Mutagen. 2004;44:74–82.PubMedCrossRefGoogle Scholar
  34. 34.
    Misra RR, Ratnasinghe D, Tangrea JA, Virtamo J, Andersen MR, Barrett M, et al. Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett. 2003;191:171–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Han S, Zhang HT, Wang Z, Xie Y, Tang R, Mao Y, et al. DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case–control studies. Eur J Hum Genet. 2006;14:1136–44.PubMedCrossRefGoogle Scholar
  36. 36.
    Sun H, Qiao Y, Zhang X, Xu L, Jia X, Sun D, et al. XRCC3 Thr241Met polymorphism with lung cancer and bladder cancer: a meta-analysis. Cancer Sci. 2010;101:1777–82.PubMedCrossRefGoogle Scholar
  37. 37.
    Araujo FD, Pierce AJ, Stark JM, Jasin M. Variant XRCC3 implicated in cancer is functional in homology-directed repair of double-strand breaks. Oncogene. 2002;21:4176–80.PubMedCrossRefGoogle Scholar
  38. 38.
    Matullo G, Palli D, Peluso M, Guarrera S, Carturan S, Celentano E, et al. XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis. 2001;22:1437–45.PubMedCrossRefGoogle Scholar
  39. 39.
    Xia WJ, Zhang YM, SU D, Shi F. Association of single nucleotide polymorphisms of DNA repair gene XRCC3-241 with non-small cell lung cancer. Zhejiang Med J. 2008;30:1291–3 [Article in Chinese].Google Scholar
  40. 40.
    Liang GY. Studies on susceptibility genes of lung cancer in chinese han population and rapid detection techniques of single nucleotide polymorphisms [D]. Southeast Univ. 2005 [Article in Chinese].Google Scholar
  41. 41.
    Liang G. Polymorphisms of DNA repair genes and carcinogen metabolizing enzymes genes and susceptibility to lung cancer [D]. Chinese Peking Union Med Coll. 2004. [Article in Chinese].Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Yun-Hua Xu
    • 1
  • Lin-Ping Gu
    • 1
  • Ying-Jia Sun
    • 1
  • Bai-Jun Cheng
    • 1
  • Shun Lu
    • 1
  1. 1.Shanghai Lung Tumor Clinic Medical CenterShanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina

Personalised recommendations