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

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Tumor Biology

Abstract

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.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Steliga MA, Dresler CM. Epidemiology of lung cancer: smoking, secondhand smoke, and genetics. Surg Oncol Clin N Am. 2011;20:605–18.

    Article  PubMed  Google Scholar 

  3. McErlean A, Ginsberg MS. Epidemiology of lung cancer. Semin Roentgenol. 2011;46:173–7.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  15. Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet. 1955;19:251–3.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  17. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  PubMed  CAS  Google Scholar 

  18. Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.

    PubMed  CAS  Google Scholar 

  19. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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].

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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].

    PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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].

    CAS  Google Scholar 

  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].

  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].

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Authors and Affiliations

  1. Shanghai Lung Tumor Clinic Medical Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, No. 241 Huaihai West Road, Shanghai, 200030, China

    Yun-Hua Xu, Lin-Ping Gu, Ying-Jia Sun, Bai-Jun Cheng & Shun Lu

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  1. Yun-Hua Xu
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Correspondence to Shun Lu.

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Xu, YH., Gu, LP., Sun, YJ. et al. No significant association between the XRCC3 Thr241Met polymorphism and lung cancer risk: a meta-analysis. Tumor Biol. 34, 865–874 (2013). https://doi.org/10.1007/s13277-012-0619-5

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  • DOI: https://doi.org/10.1007/s13277-012-0619-5

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