Skip to main content

Advertisement

SpringerLink
Log in

Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV). Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions –1082, −819, −592 by direct sequencing and IL-18 gene at position −607 and −137 by allele –specific PCR. EBV DNA serum viremia was evaluated by QC-PCR. Results: The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 –1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2–9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2–6.6). Conclusion: This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness.

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

Similar content being viewed by others

References

  1. Agarwal P, Oldenburg MC, Czarneski JE, Morse RM, Hameed MR, Cohen S, Fernandes H (2000) Comparison study for identifying promoter allelic polymorphism in interleukin 10 and tumor necrosis factor alpha genes. Diagn Mol Pathol 9:158–164

    Article  PubMed  CAS  Google Scholar 

  2. Baumforth KR, Young LS, Flavell KJ, Constantinidou C, Murray PG (1999) The Epstein-Barr virus and its association with human cancers. Mol Pathol 52:307–322

    Article  PubMed  CAS  Google Scholar 

  3. Behars OH, Henson DE, Hutter RVP, Kennedy BJ (1992) Pharynx 33–8. In: manual for staging of cancer. JB Lippincott, Philadelphia

  4. Blackwell JM (2001) Genetics and genomics in infectious disease susceptibility. Trends Mol Med 7:521–526

    Article  PubMed  CAS  Google Scholar 

  5. Breslow NE, Day NE (1980) Statistical methods in cancer research, vol I. The analysis of case-control studies. IARC Sci Publ 32:335–338

    Google Scholar 

  6. Budiani DR, Hutahaean S, Haryana SM, Soesatyo MH, Sosroseno W (2002) Interleukin-10 levels in Epstein-Barr virus-associated nasopharyngeal carcinoma. J Microbiol Immunol Infect 35:265–268

    PubMed  Google Scholar 

  7. Cardoso SM, DeFor TE, Tilley LA, Bidwell JL, Weisdorf DJ, MacMillan ML (2004) Patient interleukin-18 GCG haplotype associates with improved survival and decreased transplant-related mortality after unrelated-donor bone marrow transplantation. Br J Haematol 126:704–710

    Article  PubMed  CAS  Google Scholar 

  8. Chan KC, Zhang J, Chan AT, Lei KI, Leung SF, Chan LY, Chow KC, Lo YM (2003) Molecular characterization of circulating EBV DNA in the plasma of nasopharyngeal carcinoma and lymphoma patients. Cancer Res 63:2028–2032

    PubMed  CAS  Google Scholar 

  9. Comar M, Simonelli C, Zanussi S, De Paoli P, Vaccher E, Tirelli U, Giacca M (1997) Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection. J Clin Invest 100:893–903

    Article  PubMed  CAS  Google Scholar 

  10. Cooke GS, Hill AV (2001) Genetics of susceptibility to human infectious diseases. Nat Rev Genet 2:967–977

    Article  PubMed  CAS  Google Scholar 

  11. Crawford DH (2001) Biology and disease associations of Epstein-Barr virus. Philos Trans R Soc Lond B Biol Sci 356:461–473

    Article  PubMed  CAS  Google Scholar 

  12. Eskdale J, Kube D, Gallagher G (1996) A second polymorphic dinucleotide repeat in the 5′ flanking region of the human IL10 gene. Immunogenetics 45:82–83

    Article  PubMed  CAS  Google Scholar 

  13. Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendorp RG, Huizinga TW (1998) Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci U S A 95:9465–9470

    Article  PubMed  CAS  Google Scholar 

  14. Fliss-Jaber L, Houissa-Kastally R, Bouzouita K, Khediri N, Khelifa R (2004) Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC) patients. BMC Cancer 4(1):68–77

    Article  PubMed  CAS  Google Scholar 

  15. Fujieda S, Lee K, Sunaga H, Tsuzuki H, Ikawa H, Fan GK, Imanaka M, Takenaka H, Saito H (1999) Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma. Cancer 85:1439–1445

    Article  PubMed  CAS  Google Scholar 

  16. Giedraitis V, He B, Huang WX, Hillert J (2001) Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J Neuroimmunol 112:146–152

    Article  PubMed  CAS  Google Scholar 

  17. Haanpaa M, Nurmikko T, Hurme M (2002) Polymorphism of the IL-10 gene is associated with susceptibility to herpes zoster. Scand J Infect Dis 34:112–114

    Article  PubMed  CAS  Google Scholar 

  18. Helminen M, Kilpinen S, Virta M, Hurme M (2001) Susceptibility to primary EBV infection is associated with IL-10 gene promoter polymorphism. J Infect Dis 184:777–780

    Article  PubMed  CAS  Google Scholar 

  19. Herrmann K, Niedobitek G (2003) Epstein-Barr virus- associated carcinomas: facts and fiction. J Pathol 199:140–145

    Article  PubMed  Google Scholar 

  20. Hohler T, Kruger A, Gerken G (1998) A TNF-alpha promoter polymorphism is associated with chronic hepatitis B infection. Clin Exp Immunol 11:579–582

    Article  Google Scholar 

  21. Howell WM, Turner SJ, Bateman AC, Theaker JM (2001) IL-10 promoter polymorphisms influence tumor development in cutaneous malignant melanoma. Genes Immun 2:25–31

    Article  PubMed  CAS  Google Scholar 

  22. Hu H, Tang KF, Chua YN, Lu J, Feng P, Chew CT, Chan SH (2004) Expression of interleukin-18 by nasopharyngeal carcinoma cells: a factor that possibly initiates the massive leukocyte infiltration. Hum Pathol 35:722–728

    Article  PubMed  CAS  Google Scholar 

  23. Hurme M, Lahdenpohja N, Santtila S (1998) Gene polymorphisms of interleukins 1 and 10 in infectious and autoimmune diseases. Ann Med 30:469–73

    PubMed  CAS  Google Scholar 

  24. Janssen R, Grutters JC, Ruven HJ, Zanen P, Sato H, Welsh KI, du Bois RM, van den Bosch JM (2004) No association between interleukin-18 gene polymorphisms and haplotypes in Dutch sarcoidosis patients. Tissue Antigens 63:578–583

    Article  PubMed  CAS  Google Scholar 

  25. Karhukorpi J, Karttunen R (2001) Genotyping interleukin-10 high and low producers with single-tube bidirectional allele-specific amplification. Exp Clin Immunogenet 18:67–70

    Article  PubMed  CAS  Google Scholar 

  26. Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafe M, Cavallone L, Franceschi C, Caruso C (2002) Gender-specific association between −1082 IL-10 promoter polymorphism and longevity. Genes Immun 3:30–33

    Article  PubMed  CAS  Google Scholar 

  27. Lo YM, Chan LY, Chan A, Leung S, Lo K, Zhang J, Lee J, Hjelm M, Johnson P, Huang D (1999) Quantitative and temporal correlation between circulating cell-free EBV-DNA and tumor recurrence in nasopharingeal carcinoma. Cancer Res 59:5452–5455

    PubMed  CAS  Google Scholar 

  28. Muti G, Klersy C, Baldanti F, Granata S, Oreste P, Pezzetti L, Gatti M, Gargantini L, Caramella M, Mancini V, Gerna G, Morra E (2003) EBV load and IL-10 in EBV-positive and EBV-negative post-transplant lymphoproliferative disorders. Br J Haematol 122:927–33

    Article  PubMed  Google Scholar 

  29. Mutirangura A, Pornthanakasem W, Theamboonlers A, Sriuranpong V, Lertsanguanisinchi P, Yenrudi S, Voravud N, Suphyabun P, Poovorawan Y (1998) Epstein-Barr viral DNA in serum of patients with nasopharingeal carcinoma. Clin Cancer Res 4:665–669

    PubMed  CAS  Google Scholar 

  30. Poli F, Nocco A, Berra S, Scalamogna M, Taioli E, Longhi E, Sirchia G (2002) Allele frequencies of polymorphisms of TNFA, IL-6, IL-10 and IFNG in an Italian Caucasian population. Eur J Immunogenet 29:237–240

    Article  PubMed  CAS  Google Scholar 

  31. Pratesi C, Bortolin MT, D’Andrea M, Vaccher E, Barzan L, Bidoli E, Tedeschi R, Zanussi S, De Paoli P (2003) Quantitative plasma/serum EBV DNA load by LMP2a determination in an Italian cohort of NPC patients. J Clin Virol 28:155–164

    Article  PubMed  CAS  Google Scholar 

  32. Scola L, Crivello A, Marino V, Gioia V, Serauto A, Candore G, Colonna-Romano G, Caruso C, Lio D (2003) IL-10 and TNF-alpha polymorphisms in a sample of Sicilian patients affected by tuberculosis: implication for ageing and life span expectancy. Mech Ageing Dev 124:569–572

    Article  PubMed  CAS  Google Scholar 

  33. Shanmugaratnam K, Sobin LH (1991) Histological typing of tumors of the upper respiratory tract and ear. World Health Organization: international histological classification of tumors. Springer Berlin Heidelberg New York

    Google Scholar 

  34. Stassen NA, Breit CM, Norfleet LA, Polk HC Jr (2003) IL-18 promoter polymorphisms correlate with the development of post-injury sepsis. Surgery 134:351–356

    Article  PubMed  Google Scholar 

  35. Terwilliger JD, Ott J (1994) Linkage disequilibrium between alleles at marker loci 188–193. In: Handbook of human genetics linkage. The John Hopkins University Press, Baltimore

  36. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8

    PubMed  CAS  Google Scholar 

  37. Uboldi de Capei MU, Dametto E, Fasano ME, Rendine S, Curtoni ES (2003) Genotyping for cytokine polymorphisms: allele frequencies in the Italian population. Eur J Immunogenet 30:5–10

    Article  PubMed  CAS  Google Scholar 

  38. Vokes EE, Liebowitz DN, Weichselbaum RR (1997) Nasopharingeal carcinoma. Lancet 350:1087–1091

    Article  PubMed  CAS  Google Scholar 

  39. Wu M, Huang S, Shun T, Chang M, Lin M., Wang P, Lin J (2002) TNF-α and IL-10 promoter polymorphisms in EBV-associated gastric carcinoma. J Infect Dis 185:106–109

    Article  PubMed  CAS  Google Scholar 

  40. Yao M, Ohshima K, Suzumiya J, Kume T, Shiroshita T, Kikuchi M (1997) Interleukin-10 expression and cytotoxic-T-cell response in Epstein-Barr-virus-associated nasopharyngeal carcinoma. Int J Cancer 72:398–402

    Article  PubMed  CAS  Google Scholar 

  41. Zanussi S, Vaccher E, Caffau C, Pratesi C, Crepaldi C, Bortolin MT, Tedeschi R, Politi D, Barzan L, Tirelli U, De Paoli P (2003) Interferon-γ secretion and perforin expression are impaired in CD8+ lymphocytes from patients with UCNT. Cancer Immunol Immunother 52:28–32

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Dr. Massimo Libra for collaborating in the study with providing blood samples from healthy donors in the South of Italy; Dr. Alessia Marus for excellent laboratory technical assistance; Mrs. Luigina Mei for editing the manuscript.

Author information

Authors and Affiliations

  1. Microbiology, Immunology and Virology Unit, Centro di Riferimento Oncologico, 33081, Aviano, Italy

    Chiara Pratesi, Maria Teresa Bortolin, Rosamaria Tedeschi, Stefania Zanussi & Paolo De Paoli

  2. Epidemiology Unit, Centro di Riferimento Oncologico, 33081, Aviano, Italy

    Ettore Bidoli

  3. Medical Oncology A, Centro di Riferimento Oncologico, 33081, Aviano, Italy

    Emanuela Vaccher

  4. Immunovirology and Biotherapy Unit, Centro di Riferimento Oncologico, 33081, Aviano, Italy

    Riccardo Dolcetti & Massimo Guidoboni

  5. Radiotherapy, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy

    Gianni Franchin

  6. Ear, Nose and Throat Clinic, Hospital of Pordenone, Italy

    Luigi Barzan

  7. Department of Biopathology and Biomedical Methodologies, University of Palermo, Italy

    Calogero Caruso

Authors
  1. Chiara Pratesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Teresa Bortolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ettore Bidoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosamaria Tedeschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emanuela Vaccher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Riccardo Dolcetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Massimo Guidoboni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gianni Franchin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Luigi Barzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stefania Zanussi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Calogero Caruso
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Paolo De Paoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paolo De Paoli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pratesi, C., Bortolin, M.T., Bidoli, E. et al. Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type. Cancer Immunol Immunother 55, 23–30 (2006). https://doi.org/10.1007/s00262-005-0688-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-005-0688-z

Keywords

Search

Navigation