Skip to main content
Log in

Meta-analysis of association between cytokine gene polymorphisms and lung cancer risk

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate the association between various cytokine gene polymorphisms and lung cancer (LC) susceptibility. We searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. Totally, 20 studies involving 6,467 cases and 8,320 controls were included in the meta-analysis. The effects of eight polymorphisms, i.e. TNF-α 308G/A, IL-6 174G/C, IL-1β 31T/C, IL-1β 511C/T, COX-2 8473T/C, IL-10 1082G/A, IL-10 819C/T, and IL-10 592C/A were evaluated. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between IL-10 polymorphism and LC. For IL-10 1082G/A, the overall ORs (95% CI) of the G versus A, GG versus AA, and GG/GA versus AA were 2.35 (1.16–4.76), 2.07 (1.16–3.70) and 3.17 (1.31–7.68), respectively. For IL-10 819C/T, the pooled ORs (95% CI) of the C versus T and CC versus TT were 1.27 (1.01–1.58) and 2.27 (1.32–3.89). For IL-10 592C/A, the comparison of subjects in the CC or CC/CA genotype versus AA homozygotes showed significant results (OR = 2.00, 95% CI: 1.24–3.23; OR = 1.80, 95% CI: 1.28–2.54). But, other gene polymorphisms did not reach statistical associations. IL-10 1082G/A, 819C/T and 592C/A polymorphisms might be risk factors for LC. TNF-α 308G/A, IL-6 174G/C, IL-1β 31T/C, IL-1β 511C/T, COX-2 8473T/C polymorphisms were not detected to be related to the risk for LC. Due to the limitation of the number of the studies, we should take the conclusion with caution. While, further studies are necessary for more precise association.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Boyle P, Dresler C (2005) Preventing the lung cancer epidemic. Ann Oncol 16(10):1565–1566

    Article  PubMed  CAS  Google Scholar 

  2. Farjadfar A, Mojtahedi Z, Ghayumi MA et al (2009) Interleukin-18 promoter polymorphism is associated with lung cancer: a case-control study. Acta Oncol 48(7):971–976

    Article  PubMed  CAS  Google Scholar 

  3. Witschi H (2001) A short history of lung cancer. Toxicol Sci 64(1):4–6

    Article  PubMed  CAS  Google Scholar 

  4. Esposito L, Conti D, Ailavajhala R et al (2010) Lung cancer: are we up to the challenge? Curr Genomics 11(7):513–518

    Article  PubMed  CAS  Google Scholar 

  5. Hecht SS (1999) Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 91(14):1194–1210

    Article  PubMed  CAS  Google Scholar 

  6. Purdue MP, Hoppin JA, Blair A et al (2006) Occupational exposure to organochlorine insecticides and cancer incidence in the agricultural health study. Int J Cancer 120:642–649

    Article  Google Scholar 

  7. Sorahan T, Williams SP (2005) Mortality of workers at a nickel carbonyl refinery, 1958–2000. Occup Environ Med 62(2):80–85

    Article  PubMed  CAS  Google Scholar 

  8. Biggeri A, Barbone F, Lagazio C et al (1996) Air pollution and lung cancer in Trieste, Italy: spatial analysis of risk as a function of distance from sources. Environ Health Perspect 104(7):750–754

    Article  PubMed  CAS  Google Scholar 

  9. Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87(6):2095–2147

    PubMed  CAS  Google Scholar 

  10. Brichory FM, Misek DE, Yim AM, Krause MC et al (2001) An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer. Proc Natl Acad Sci USA 98(17):9824–9829

    Article  PubMed  CAS  Google Scholar 

  11. Bazzoni F, Beutler B (1996) The tumor necrosis factor ligand and receptor families. N Engl J Med 334(26):1717–1725

    Article  PubMed  CAS  Google Scholar 

  12. Wilson AG, Symons JA, McDowell TL et al (1997) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 94(7):3195–3199

    Article  PubMed  CAS  Google Scholar 

  13. Koki A, Khan NK, Woerner BM et al (2002) Cyclooxygenase-2 in human pathological disease. Adv Exp Med Biol 507:177–184

    Article  PubMed  CAS  Google Scholar 

  14. Bi N, Yang M, Zhang L et al (2010) Cyclooxygenase-2 genetic variants are associated with survival in unresectable locally advanced non-small cell lung cancer. Clin Cancer Res 16(8):2383–2390

    Article  PubMed  CAS  Google Scholar 

  15. Hida T, Yatabe Y, Achiwa H et al (1998) Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 58:3761–3764

    PubMed  CAS  Google Scholar 

  16. Beretta L, Cappiello F, Barili M et al (2007) Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis. Tissue Antigens 69(4):305–312

    Article  PubMed  CAS  Google Scholar 

  17. Shih CM, Lee YL, Chiou HL et al (2005) The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer. Lung Cancer 50(3):291–297

    Article  PubMed  Google Scholar 

  18. Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629–634

    Article  CAS  Google Scholar 

  19. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–102

    Article  Google Scholar 

  20. Banerjee I (2010) Relationship between Paraoxonase 1 (PON1) gene polymorphisms and susceptibility of stroke: a meta-analysis. Eur J Epidemiol 25(7):449–458

    Article  PubMed  CAS  Google Scholar 

  21. Beger C, Berlin JA (1988) Publication bias: a problem in interpreting medical data. J R Stat Soc A 151:419–463

    Article  Google Scholar 

  22. Liu CJ, Hsia TC, Wang RF et al (2010) Interaction of cyclooxygenase 2 genotype and smoking habit in Taiwanese lung cancer patients. Anticancer Res 30(4):1195–1199

    PubMed  CAS  Google Scholar 

  23. Colakogullari M, Ulukaya E, Yilmaztepe Oral A et al (2008) The involvement of IL-10, IL-6, IFN-gamma, TNF-alpha and TGF-beta gene polymorphisms among Turkish lung cancer patients. Cell Biochem Funct 26(3):283–290

    Article  PubMed  CAS  Google Scholar 

  24. Seifart C, Plagens A, Dempfle A et al (2005) TNF-alpha, TNF-beta, IL-6, and IL-10 polymorphisms in patients with lung cancer. Dis Markers 21(3):157–165

    PubMed  CAS  Google Scholar 

  25. Huang Y, Bi Y, Luo M et al (2005) TNF-alpha gene polymorphism in patients with lung squamous carcinoma. Natl Med J China 85(15):1064–1065

    CAS  Google Scholar 

  26. Stankovic MM, Nestorovic AR, Tomovic AM et al (2009) TNF-alpha-308 promoter polymorphism in patients with chronic obstructive pulmonary disease and lung cancer. Neoplasma 56(4):348–352

    Article  PubMed  CAS  Google Scholar 

  27. Shih CM, Lee YL, Chiou HL et al (2006) Association of TNF-alpha polymorphism with susceptibility to and severity of non-small cell lung cancer. Lung Cancer 52(1):15–20

    Article  PubMed  Google Scholar 

  28. Flego V, Radojcić Badovinac A, Bulat-Kardum L et al (2009) Primary lung cancer and TNF-alpha gene polymorphisms: a case-control study in a Croatian population. Med Sci Monit 15(7):CR361–CR365

    PubMed  CAS  Google Scholar 

  29. Campa D, Hung RJ, Mates D et al (2005) Lack of association between polymorphisms in inflammatory genes and lung cancer risk. Cancer Epidemiol Biomarkers Prev 14(2):538–539

    Article  PubMed  CAS  Google Scholar 

  30. Campa D, Zienolddiny S, Maggini V et al (2004) Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis 25(2):229–235

    Article  PubMed  CAS  Google Scholar 

  31. Vogel U, Christensen J, Wallin H et al (2008) Polymorphisms in genes involved in the inflammatory response and interaction with NSAID use or smoking in relation to lung cancer risk in a prospective study. Mutat Res 639(1–2):89–100

    PubMed  CAS  Google Scholar 

  32. Lim WY, Chen Y, Mohamed Ali S et al (2011) Polymorphisms in inflammatory pathway genes, host factors and lung cancer risk in Chinese female never-smokers. Carcinogenesis 32(4):522–529

    Article  PubMed  CAS  Google Scholar 

  33. Zienolddiny S, Ryberg D, Maggini V et al (2004) Polymorphisms of the interleukin-1 beta gene are associated with increased risk of non-small cell lung cancer. Int J Cancer 109(3):353–356

    Article  PubMed  CAS  Google Scholar 

  34. Wu KS, Zhou X, Zheng F et al (2010) Influence of interleukin-1 beta genetic polymorphism, smoking and alcohol drinking on the risk of non-small cell lung cancer. Clin Chim Acta 411(19–20):1441–1446

    Article  PubMed  CAS  Google Scholar 

  35. Lee KM, Shen M, Chapman RS et al (2007) Polymorphisms in immunoregulatory genes, smoky coal exposure and lung cancer risk in Xuan Wei, China. Carcinogenesis 28(7):1437–1441

    Article  PubMed  CAS  Google Scholar 

  36. Hao M, Wang W, Ye L et al (2009) Association of genetic polymorphism within promoter region of TNF-a, IL-1β and IL-10 with the susceptibility to lung cancer. J Environ Occup Med 26(1):24–27

    Google Scholar 

  37. Asada M, Yasuda H, Ebihara S et al (2006) Interleukin-1beta gene polymorphisms associated with risk of lung cancer in Japanese. Lung Cancer 54(2):261–263

    Article  PubMed  Google Scholar 

  38. Park JM, Choi JE, Chae MH (2006) Relationship between cyclooxygenase 8473T>C polymorphism and the risk of lung cancer: a case-control study. BMC Cancer 6:70

    Article  PubMed  Google Scholar 

  39. Hu Z, Miao X, Ma H et al (2005) A common polymorphism in the 3′UTR of cyclooxygenase 2/prostaglandin synthase 2 gene and risk of lung cancer in a Chinese population. Lung Cancer 48(1):11–17

    Article  PubMed  CAS  Google Scholar 

  40. Sørensen M, Autrup H, Tjønneland A et al (2005) A genetic polymorphism in prostaglandin synthase 2 (8473, T→C) and the risk of lung cancer. Cancer Lett 226(1):49–54

    Article  PubMed  Google Scholar 

  41. de Waal Malefyt R, Abrams J, Benett B, Figdor CG, de Vries J (1991) Interleukin 10 (IL-10) inhibits cytokine synthesis by human monozytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–1220

    Article  PubMed  Google Scholar 

  42. Kiyohara C, Yoshimasu K (2007) Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis. Int J Med Sci 4(2):59–71

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partly supported by the grants from the Cademic Leader Foundation of Anhui Medical University, Doctor’s Scientific Research Foundation of Anhui Medical University (Code:XJ200907), and early training in research of seven-year-program clinical medicine of Anhui Medical University (code: 2010-ZQKY-17, 2010-ZQKY-18).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jing Wang.

Additional information

Wen-jia Peng and Qian He contributed equally to this work and should be considered co-first authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 155 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peng, Wj., He, Q., Yang, Jx. et al. Meta-analysis of association between cytokine gene polymorphisms and lung cancer risk. Mol Biol Rep 39, 5187–5194 (2012). https://doi.org/10.1007/s11033-011-1315-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-1315-z

Keywords

Navigation