Skip to main content

Advertisement

SpringerLink
Log in

Interleukin-12B rs3212227 polymorphism and cancer risk: a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

IL-12 plays a very important role in the development and progress of cancer. IL-12B rs3212227 polymorphism has been reported and many studies have focused on the role of this polymorphism in various cancers. However, the association between IL-12B rs3212227 polymorphism and cancer risk remains controversial. Therefore, we performed a systematic meta-analysis to estimate the overall cancer risk associated with this gene polymorphism and to quantify any potential between-study heterogeneity. PubMed and Embase databases were searched for case–control studies published up to April 1, 2012 that investigated IL-12B rs3212227 polymorphism and cancer risk. Odds ratios (OR) with 95 % confidence intervals (95 % CI) were used to access the strength of this association. Heterogeneity among articles and publication bias were also verified. Ten studies with 2,954 cancer patients and 3,276 healthy controls were included. This meta-analysis showed that there was a significant association between IL-12B rs3212227 polymorphism and overall cancer risk (CC/AC vs AA: OR = 1.32, 95 % CI = 1.06–1.63). When stratified by cancer type, we found a significant increased risk in cervical and nasopharyngeal cancer (OR = 1.34, 95 % CI = 1.04–1.73; OR = 2.03, 95 % CI = 1.57–2.63, respectively). In the stratified analysis, we also observed a similar association in population-based studies (OR = 1.34, 95 % CI = 1.00–1.80), Asian populations (OR = 1.33, 95 % CI = 1.06–1.67) and European populations (OR = 1.54, 95 % CI = 1.04–2.28). According to the results of our meta-analysis, IL-12B rs3212227 polymorphism probably is associated with a high risk of cancer.

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. Pharoah PD, Dunning AM, Ponder BA, Easton DF (2004) Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 4:850–860

    Article  PubMed  CAS  Google Scholar 

  2. Xu M, Mizoguchi I, Morishima N, Chiba Y, Mizuguchi J et al (2010) Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27. Clin Dev Immunol 2010:9

  3. Huang D, Cancilla MR, Morahan G (2000) Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Genes Immun 1:515–520

    Article  PubMed  CAS  Google Scholar 

  4. Mailliard RB, Son YI, Redlinger R, Coates PT, Giermasz A et al (2003) Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. J Immunol 171:2366–2373

    PubMed  CAS  Google Scholar 

  5. Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146

    Article  PubMed  CAS  Google Scholar 

  6. Boniface K, Blom B, Liu YJ, de Waal MR (2008) From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. Immunol Rev 226:132–146

    Article  PubMed  CAS  Google Scholar 

  7. Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR et al (1993) Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 178:1223–1230

    Article  PubMed  CAS  Google Scholar 

  8. Noguchi Y, Jungbluth A, Richards EC, Old LJ (1996) Effect of interleukin 12 on tumor induction by 3-methylcholanthrene. Proc Natl Acad Sci USA 93:11798–11801

    Article  PubMed  CAS  Google Scholar 

  9. Nanni P, Nicoletti G, De Giovanni C, Landuzzi L, Di Carlo E et al (2001) Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice. J Exp Med 194:1195–1205

    Article  PubMed  CAS  Google Scholar 

  10. Murakami S, Okubo K, Tsuji Y, Sakata H, Hamada S et al (2004) Serum interleukin-12 levels in patients with gastric cancer. Surg Today 34:1014–1019

    Article  PubMed  CAS  Google Scholar 

  11. Miteva L, Stanilov N, Deliysky T, Mintchev N, Stanilova S (2009) Association of polymorphisms in regulatory regions of interleukin-12p40 gene and cytokine serum level with colorectal cancer. Cancer Invest 27:924–931

    Article  PubMed  CAS  Google Scholar 

  12. Motzer RJ, Rakhit A, Thompson JA, Nemunaitis J, Murphy BA et al (2001) Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma. J Interferon Cytokine Res 21:257–263

    Article  PubMed  CAS  Google Scholar 

  13. Weiss GR, O’Donnell MA, Loughlin K, Zonno K, Laliberte RJ et al (2003) Phase 1 study of the intravesical administration of recombinant human interleukin-12 in patients with recurrent superficial transitional cell carcinoma of the bladder. J Immunother 26:343–348

    Article  PubMed  CAS  Google Scholar 

  14. van Herpen CM, van der Laak JA, de Vries IJ, van Krieken JH, de Wilde PC et al (2005) Intratumoral recombinant human interleukin-12 administration in head and neck squamous cell carcinoma patients modifies locoregional lymph node architecture and induces natural killer cell infiltration in the primary tumor. Clin Cancer Res 11:1899–1909

    Article  PubMed  Google Scholar 

  15. Ryu CH, Park SH, Park SA, Kim SM, Lim JY et al (2011) Gene therapy of intracranial glioma using interleukin 12-secreting human umbilical cord blood-derived mesenchymal stem cells. Hum Gene Ther 22:733–743

    Article  PubMed  CAS  Google Scholar 

  16. Stanilova S, Miteva L (2005) Taq-I polymorphism in 3′UTR of the IL-12B and association with IL-12p40 production from human PBMC. Genes Immun 6:364–366

    Article  PubMed  CAS  Google Scholar 

  17. Morahan G, Huang D, Ymer SI, Cancilla MR, Stephen K et al (2001) Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet 27:218–221

    Article  PubMed  CAS  Google Scholar 

  18. Zhao B, Meng LQ, Huang HN, Pan Y, Xu QQ (2009) A novel functional polymorphism, 16974 A/C, in the interleukin-12-3′ untranslated region is associated with risk of glioma. DNA Cell Biol 28:335–341

    Article  PubMed  CAS  Google Scholar 

  19. Hirota T, Suzuki Y, Hasegawa K, Obara K, Matsuda A et al (2005) Functional haplotypes of IL-12B are associated with childhood atopic asthma. J Allergy Clin Immunol 116:789–795

    Article  PubMed  CAS  Google Scholar 

  20. Howell WM, Turner SJ, Theaker JM, Bateman AC (2003) Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma. Eur J Immunogenet 30:409–414

    Article  PubMed  CAS  Google Scholar 

  21. Han SS, Cho EY, Lee TS, Kim JW, Park NH et al (2008) Interleukin-12 p40 gene (IL12B) polymorphisms and the risk of cervical cancer in Korean women. Eur J Obstet Gynecol Reprod Biol 140:71–75

    Article  PubMed  CAS  Google Scholar 

  22. Wei YS, Lan Y, Luo B, Lu D, Nong HB (2009) Association of variants in the interleukin-27 and interleukin-12 gene with nasopharyngeal carcinoma. Mol Carcinog 48:751–757

    Article  PubMed  CAS  Google Scholar 

  23. Chen X, Han S, Wang S, Zhou X, Zhang M et al (2009) Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clin Cancer Res 15:400–405

    Article  PubMed  CAS  Google Scholar 

  24. Ben CA, Busson M, Douik H, Boukouaci W, Mamoghli T et al (2011) Association of IL-12p40 +1188 A/C polymorphism with nasopharyngeal cancer risk and tumor extension. Tissue Antigens 78:148–151

    Article  Google Scholar 

  25. Liu L, Xu Y, Liu Z, Chen J, Zhang Y et al (2011) IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. Int J Cancer 128:1692–1696

    Article  PubMed  CAS  Google Scholar 

  26. Huang ZQ, Wang JL, Pan GG, Wei YS (2012) Association of single nucleotide polymorphisms in IL-12 and IL-27 genes with colorectal cancer risk. Clin Biochem 45:54–59

    Article  PubMed  CAS  Google Scholar 

  27. Sima X, Xu J, Li Q, Luo L, Liu J et al (2012) Gene-gene interactions between interleukin-12A and interleukin-12B with the risk of brain tumor. DNA Cell Biol 31:219–223

    Article  PubMed  CAS  Google Scholar 

  28. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  29. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  30. Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24:1291–1306

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Dadao Road, Wuhan, 430030, China

    Huilong Chen, Sheng Cheng, Jianmiao Wang, Hansvin Bunjhoo, Weining Xiong & Yongjian Xu

  2. Department of Respiratory Medicine, Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, China

    Chao Cao

Authors
  1. Huilong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheng Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianmiao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chao Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hansvin Bunjhoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Weining Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yongjian Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yongjian Xu.

Additional information

Huilong Chen and Sheng Cheng have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, H., Cheng, S., Wang, J. et al. Interleukin-12B rs3212227 polymorphism and cancer risk: a meta-analysis. Mol Biol Rep 39, 10235–10242 (2012). https://doi.org/10.1007/s11033-012-1899-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1899-y

Keywords

Search

Navigation