Tumor Biology

, Volume 35, Issue 7, pp 6665–6671 | Cite as

Genetic polymorphism of APE1 rs1130409 can contribute to the risk of lung cancer

  • Feng Jin
  • Chengyuan Qian
  • Yi Qing
  • Zhimin Zhang
  • Ge Wang
  • Jinlu Shan
  • Nan Dai
  • Zheng Li
  • Dong WangEmail author
Research Article


Accumulative evidence suggests that polymorphism in the APE1 gene may have association with the etiology of lung cancer by modulating DNA repair capacity. Many studies have evaluated the association with great discrepancies in the results. The present meta-analysis was undertaken to clarify the effects of this polymorphism on lung cancer. A meta-analysis of 15 studies with 4,932 lung cancer patients and 6,555 cancer-free controls was conducted to evaluate the strength of the association using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, no significant association was found between APE1 polymorphism and lung cancer risk. We also did not observe any statistical evidence of modified lung cancer risk either in smokes or in nonsmokers. In the stratified analysis by ethnicity, however, it was found that the Glu/Clu genotype carriers had 1.16-fold higher risk of suffering lung cancer compared with the carriers of Arg/Glu + Arg/Arg genotypes in Asian population (OR = 1.16, 95 % CI = 1.01-1.32, P = 0.242). This meta-analysis provides statistical evidence for a potential association between APE1 polymorphism and an increased risk of lung cancer in Asian population.

Key words

APE1 Polymorphism Lung cancer Meta-analysis 



Financial support was provided by China NSFC: The effect and mechanism of APE1 in angiogenesis after radiotherapy (No. 30901747).

Conflicts of interest



  1. 1.
    Parkin DM et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94(2):153–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Rong B et al. Systematic review and meta-analysis of Endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer. World J Surg Oncol. 2012;10:170.CrossRefPubMedGoogle Scholar
  3. 3.
    Fucic A et al. Lung cancer and environmental chemical exposure: a review of our current state of knowledge with reference to the role of hormones and hormone receptors as an increased risk factor for developing lung cancer in man. Toxicol Pathol. 2010;38(6):849–55.CrossRefPubMedGoogle Scholar
  4. 4.
    Steliga MA, Dresler CM. Epidemiology of lung cancer: smoking, secondhand smoke, and genetics. Surg Oncol Clin N Am. 2011;20(4):605–18.CrossRefPubMedGoogle Scholar
  5. 5.
    Shields PG. Molecular epidemiology of smoking and lung cancer. Oncogene. 2002;21(45):6870–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Shields PG, Harris CC. Cancer risk and low-penetrance susceptibility genes in gene-environment interactions. J Clin Oncol. 2000;18(11):2309–15.PubMedGoogle Scholar
  7. 7.
    Spitz MR et al. Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev. 2003;12(8):689–98.PubMedGoogle Scholar
  8. 8.
    Ito H et al. Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk. Carcinogenesis. 2004;25(8):1395–401.CrossRefPubMedGoogle Scholar
  9. 9.
    Lu AL et al. Repair of oxidative DNA damage: mechanisms and functions. Cell Biochem Biophys. 2001;35(2):141–70.CrossRefPubMedGoogle Scholar
  10. 10.
    Izumi T et al. Requirement for human AP endonuclease 1 for repair of 3′-blocking damage at DNA single-strand breaks induced by reactive oxygen species. Carcinogenesis. 2000;21(7):1329–34.CrossRefPubMedGoogle Scholar
  11. 11.
    Tell G et al. The intracellular localization of APE1/Ref-1: more than a passive phenomenon? Antioxid Redox Signal. 2005;7(3–4):367–84.CrossRefPubMedGoogle Scholar
  12. 12.
    Xi T, Jones IM, Mohrenweiser HW. Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function. Genomics. 2004;83(6):970–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Hadi MZ et al. Functional characterization of Ape1 variants identified in the human population. Nucleic Acids Res. 2000;28(20):3871–9.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Agachan B et al. Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking. Anticancer Res. 2009;29(6):2417–20.PubMedGoogle Scholar
  15. 15.
    Misra RR 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(2):171–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Li Z et al. Genetic polymorphism of DNA base-excision repair genes (APE1, OGG1 and XRCC1) and their correlation with risk of lung cancer in a Chinese population. Arch Med Res. 2011;42(3):226–34.CrossRefPubMedGoogle Scholar
  17. 17.
    Chen WC et al. The contribution of DNA apurinic/apyrimidinic endonuclease genotype and smoking habit to Taiwan lung cancer risk. Anticancer Res. 2013;33(6):2775–8.PubMedGoogle Scholar
  18. 18.
    De Ruyck K et al. Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res. 2007;631(2):101–10.CrossRefPubMedGoogle Scholar
  19. 19.
    Higgins JP et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefPubMedGoogle Scholar
  21. 21.
    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.PubMedGoogle Scholar
  22. 22.
    Egger M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Popanda O et al. Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis. 2004;25(12):2433–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Shen M et al. Polymorphisms in the DNA base excision repair genes APEX1 and XRCC1 and lung cancer risk in Xuan Wei. China Anticancer Res. 2005;25(1B):537–42.PubMedGoogle Scholar
  25. 25.
    Matullo G et al. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis. 2006;27(5):997–1007.CrossRefPubMedGoogle Scholar
  26. 26.
    Zienolddiny S et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2006;27(3):560–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Lu J et al. Functional characterization of a promoter polymorphism in APE1/Ref-1 that contributes to reduced lung cancer susceptibility. FASEB J. 2009;23(10):3459–69.CrossRefPubMedGoogle Scholar
  28. 28.
    Lo YL et al. A polymorphism in the APE1 gene promoter is associated with lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18(1):223–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Osawa K et al. APEX1 Asp148Glu gene polymorphism is a risk factor for lung cancer in relation to smoking in Japanese. Asian Pac J Cancer Prev. 2010;11(5):1181–6.PubMedGoogle Scholar
  30. 30.
    Deng Q et al. Genetic polymorphisms in ATM, ERCC1, APE1 and iASPP genes and lung cancer risk in a population of southeast China. Med Oncol. 2011;28(3):667–72.CrossRefPubMedGoogle Scholar
  31. 31.
    Pan H et al. Contributory role of five common polymorphisms of RAGE and APE1 genes in lung cancer among Han Chinese. PLoS One. 2013;8(7):e69018.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Fortini P et al. The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie. 2003;85(11):1053–71.CrossRefPubMedGoogle Scholar
  33. 33.
    Wei Q et al. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst. 2000;92(21):1764–72.CrossRefPubMedGoogle Scholar
  34. 34.
    Shen H et al. Smoking, DNA repair capacity and risk of nonsmall cell lung cancer. Int J Cancer. 2003;107(1):84–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Mohrenweiser HW et al. Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans. Cancer Epidemiol Biomarkers Prev. 2002;11(10 Pt 1):1054–64.PubMedGoogle Scholar
  36. 36.
    Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11(12):1513–30.PubMedGoogle Scholar
  37. 37.
    Qiao Y et al. Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res. 2002;509(1–2):165–74.CrossRefPubMedGoogle Scholar
  38. 38.
    Karahalil B, Bohr VA, Wilson 3rd DM. Impact of DNA polymorphisms in key DNA base excision repair proteins on cancer risk. Hum Exp Toxicol. 2012;31(10):981–1005.CrossRefPubMedGoogle Scholar
  39. 39.
    Ji YN et al. APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis. Mol Biol Rep. 2011;38(7):4537–43.CrossRefPubMedGoogle Scholar
  40. 40.
    Wei W et al. Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis. Mol Biol Rep. 2012;39(12):11249–62.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Feng Jin
    • 1
  • Chengyuan Qian
    • 1
  • Yi Qing
    • 1
  • Zhimin Zhang
    • 1
  • Ge Wang
    • 1
  • Jinlu Shan
    • 1
  • Nan Dai
    • 1
  • Zheng Li
    • 1
  • Dong Wang
    • 1
    Email author
  1. 1.Cancer Center, Research Institute of Surgery and Daping HospitalThird Military Medical UniversityChongqingChina

Personalised recommendations