Skip to main content
SpringerLink
Log in

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

  • Research Article
  • Published:
Tumor Biology

Abstract

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.

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

Similar content being viewed by others

References

  1. Parkin DM et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94(2):153–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  4. Steliga MA, Dresler CM. Epidemiology of lung cancer: smoking, secondhand smoke, and genetics. Surg Oncol Clin N Am. 2011;20(4):605–18.

    Article  PubMed  Google Scholar 

  5. Shields PG. Molecular epidemiology of smoking and lung cancer. Oncogene. 2002;21(45):6870–6.

    Article  CAS  PubMed  Google Scholar 

  6. Shields PG, Harris CC. Cancer risk and low-penetrance susceptibility genes in gene-environment interactions. J Clin Oncol. 2000;18(11):2309–15.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  9. Lu AL et al. Repair of oxidative DNA damage: mechanisms and functions. Cell Biochem Biophys. 2001;35(2):141–70.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  13. Hadi MZ et al. Functional characterization of Ape1 variants identified in the human population. Nucleic Acids Res. 2000;28(20):3871–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  19. Higgins JP et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

    Article  PubMed Central  PubMed  Google Scholar 

  20. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  22. Egger M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  25. Matullo G et al. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis. 2006;27(5):997–1007.

    Article  CAS  PubMed  Google Scholar 

  26. Zienolddiny S et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2006;27(3):560–7.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Fortini P et al. The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie. 2003;85(11):1053–71.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  34. Shen H et al. Smoking, DNA repair capacity and risk of nonsmall cell lung cancer. Int J Cancer. 2003;107(1):84–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  39. Ji YN et al. APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis. Mol Biol Rep. 2011;38(7):4537–43.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Cancer Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, No.10 Changjiang Zhilu, Yuzhong District, Chongqing, 400042, China

    Feng Jin, Chengyuan Qian, Yi Qing, Zhimin Zhang, Ge Wang, Jinlu Shan, Nan Dai, Zheng Li & Dong Wang

Authors
  1. Feng Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chengyuan Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Qing
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhimin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ge Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jinlu Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nan Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dong Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jin, F., Qian, C., Qing, Y. et al. Genetic polymorphism of APE1 rs1130409 can contribute to the risk of lung cancer. Tumor Biol. 35, 6665–6671 (2014). https://doi.org/10.1007/s13277-014-1829-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1829-9

Key words

Search

Navigation