Skip to main content

Advertisement

SpringerLink
Log in

TNF-α and IL-10 promoter polymorphisms, HPV infection, and cervical cancer risk

  • Research Article
  • Published:
Tumor Biology

Abstract

Although the implication of genetic factors in cervical cancer development remains to be elucidated, accumulative epidemiological evidence suggests that polymorphisms of cytokine genes may be involved in the etiology of cervical carcinoma. Tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) are two multifunctional cytokines implicated in inflammation, immunity, and cellular organization, and were proposed to play important roles in cancer biology. In order to determine whether IL-10 -1082 (G/A) and TNF-α -238 (G/A) and -308 (G/A) polymorphisms are associated with susceptibility to cervical cancer, a case–control study of 122 cancer patients and 176 healthy controls was conducted. Cervical samples were genotyped for both TNF-α polymorphisms by PCR-RFLP assay. SNP-1082 from IL-10 gene was genotyped using pyrosequencing technology. The association between cervical cancer risk and the studied SNPs was evaluated by logistic regression. Under univariate analysis, none of these polymorphisms appeared associated with susceptibility of cervical cancer development or HPV infection. However, individuals carrying heterozygous genotype for TNF-α -238 polymorphism seem to be at lower risk for cervical cancer development, with borderline significance (OR = 0.42, P = 0.069), as well as those carrying heterozygous genotypes for IL-10 and TNF-α -238 (OR = 0.40, P = 0.08). In conclusion, these results suggest a potential effect of TNF-α -238 G/A in the reduction of cervical cancer risk in Argentine women, but not TNF-α -308 or IL-10. Larger studies are needed to fully understand the genetic predisposition for the development of cervical 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

Similar content being viewed by others

References

  1. Cogliano V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F. WHO International Agency for Research on Cancer (2005). Carcinogenicity of human papillomaviruses. Lancet Oncol. 2005;6:204.

    Article  PubMed  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  3. Muñoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348:518–27.

    Article  PubMed  Google Scholar 

  4. Hemminki K, Dong C, Vaittinen P. Familial risks in cervical cancer: is there a hereditary component? Int J Cancer. 1999;82:775–81.

    Article  CAS  PubMed  Google Scholar 

  5. Horng JT, Hu KC, Wu LC, et al. Identifying the combination of genetic factors that determine susceptibility to cervical cancer. IEEE Trans Inf Technol Biomed. 2004;8:59–66.

    Article  PubMed  Google Scholar 

  6. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342–50.

    Article  CAS  PubMed  Google Scholar 

  7. Kadish AS, Ho GY, Burk RD, et al. Lymphoproliferative responses to human papillomavirus (HPV) type 16 proteins E6 and E7: outcome of HPV infection and associated neoplasia. J Natl Cancer Inst. 1997;89:1285–93.

    Article  CAS  PubMed  Google Scholar 

  8. Clerici M, Merola M, Ferrario E, et al. Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection. J Natl Cancer Inst. 1997;89:245–50.

    Article  CAS  PubMed  Google Scholar 

  9. Tartour E, Gey A, Sastsre-Garou X, Lombard Surin I, Mosseri V, Fridman WH. Prognostic value of intratumoral interferon gamma messenger RNA expression in invasive cervical carcinomas. J Natl Cancer Inst. 1998;90:287–94.

    Article  CAS  PubMed  Google Scholar 

  10. Tartour E, Pannetier C, Mathiot C, et al. Prognostic value of cytokine and Fc gamma receptor assays in oncology. Immunol Lett. 1995;44:145–8.

    Article  CAS  PubMed  Google Scholar 

  11. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;38:423–8.

    Article  Google Scholar 

  12. Li H, Groop L, Nilsson A, Weng J, Tuomi T. A combination of human leukocyte antigen DQB1*02 and the tumor necrosis factor alpha promoter G308A polymorphism predisposes to an insulin-deficient phenotype in patients with type 2 diabetes. J Clin Endocr Metab. 2003;88:2767–74.

    Article  CAS  PubMed  Google Scholar 

  13. Pillai S, Bikle DD, Eessalu TE, Aggarwal BB, Elias PM. Binding and biological effects of tumor necrosis factor alpha on cultured human neonatal foreskin keratinocytes. J Clin Invest. 1989;83:816–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Eksteen JA, Scott PA, Perry I, Jankowski JA. Inflammation promotes Barretts metaplasia and cancer: a unique role for TNF alpha. Eur J Cancer Prev. 2001;10:163–6.

    Article  CAS  PubMed  Google Scholar 

  15. Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol. 1997;34:391–9.

    Article  CAS  PubMed  Google Scholar 

  16. Wilson AG, Symons JA, McDowell TL, McDevitt HQ, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997;94:3195–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Höhler T, Kruger A, Gerken G, Schneider PM, Meyer zum Büschenfelde KH, Rittner C. Tumor necrosis factor alpha promoter polymorphism at position -238 is associated with chronic active hepatitis C infection. J Med Virol. 1998;54:173–7.

    Article  PubMed  Google Scholar 

  18. Jang WH, Yang YI, Yea SS, et al. The -238 tumor necrosis factor-alpha promoter polymorphism is associated with decreased susceptibility to cancers. Cancer Lett. 2001;166:41–6.

    Article  CAS  PubMed  Google Scholar 

  19. Strieter RM, Kunkel SL, Bone RC. Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med. 1993;21:S447–63.

    Article  CAS  PubMed  Google Scholar 

  20. Ardizzoia A, Lissoni P, Brivio F, et al. Tumor necrosis factor in solid tumors: increased blood levels in the metastasic disease. J Biol Regul Homeost Agents. 1992;6:103–7.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  22. Alamartine E, Berthoux P, Mariat C, Cambazard F, Berthoux F. Interleukin-10 promoter polymorphisms and susceptibility to skin squamous cell carcinoma after renal transplantation. J Invest Derm. 2003;120:99–103.

    Article  PubMed  Google Scholar 

  23. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ting Y, Manos MM. Detection and typing of genital human Papillomavirus. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ, editors. PCR protocols. San Diego: Academic Pres; 1990. p. 356.

    Google Scholar 

  25. Evander M, Edlund K, Bodun E, et al. Comparison of a one-step and two-step polimerase chain reaction with degenerate general primers in a population-based study of human papillomavirus infection in young Swedish women. J Clin Microbiol. 1992;30:987–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Söderlund-Strand A, Rymark P, Andersson P, Dillner J, Dillner L. Comparison between the Hybrid Capture II Test and a PCR-Based Human Papillomavirus detection method for diagnosis and posttreatment follow-up of cervical intraepithelial neoplasia. J Clin Microbiol. 2005;43:3260–6.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Stanczuk GA, Sibanda EN, Perrey C, et al. Cancer of the uterine cervix may be significantly associated with a gene polymorphism coding for increased IL-10 production. Int J Cancer. 2001;94:792–4.

    Article  CAS  PubMed  Google Scholar 

  28. Deshpande A, Nolan JP, White PS, et al. TNF-alpha promoter polymorphisms and susceptibility to human papillomavirus 16-associated cervical cancer. J Infect Dis. 2005;191:969–76.

    Article  CAS  PubMed  Google Scholar 

  29. Kirkpatrick A, Bidwell J, van den Brule AJ, Meijer CJ, Pawade J, Glew S. TNF alpha polymorphism frequencies in HPV-associated cervical dysplasia. Gynecol Oncol. 2004;92:675–9.

    Article  CAS  PubMed  Google Scholar 

  30. Liu L, Yang X, Chen X, et al. Association between TNF-α polymorphisms and cervical cancer risk: a meta-analysis. Mol Biol Rep. 2012;39:2683–8.

    Article  CAS  PubMed  Google Scholar 

  31. Badano I, Stietz SM, Schurr TG, et al. Analysis of TNF-α promoter SNPs and the risk of cervical cancer in urban populations of Posadas (Misiones, Argentina). J Clin Virol. 2012;53:54–9.

    Article  CAS  PubMed  Google Scholar 

  32. Govan VA, Constant D, Hoffman M, Williamson AL. The allelic distribution of -308 tumor necrosis factor-alpha gene polymorphism in South African women with cervical cancer and control women. BMC Cancer. 2006;6:24.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Stanczuk GA, Sibanda EN, Tswana SA, Bergstrom S. Polymorphism at the -308-promoter position of the tumor necrosis factor-alpha (TNF-alpha) gene and cervical cancer. Int J Gynecol Cancer. 2003;13:148–53.

    Article  CAS  PubMed  Google Scholar 

  34. Ivansson EL, Juko-Pecirep I, Gyllensten UB. Interaction of immunological genes on chromosome 2q33 and IFNG in susceptibility to cervical cancer. Gynecol Oncol. 2010;116:544–8.

    Article  CAS  PubMed  Google Scholar 

  35. Calhoun ES, McGovern RM, Janney CA, et al. Host genetic polymorphism analysis in cervical cancer. Clin Chem. 2002;48:1218–24.

    CAS  PubMed  Google Scholar 

  36. Magalhães RF, Biral AC, Pancoto JA, et al. Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha -238 and -308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study. Int J Dermatol. 2010;49:1133–40.

    Article  PubMed  Google Scholar 

  37. Nedoszytko B, Szczerkowska-Dobosz A, Zabłotna M, Gleń J, Rebała K, Roszkiewicz J. Associations of promoter region polymorphisms in the tumour necrosis factor-alpha gene and early-onset psoriasis vulgaris in a northern Polish population. Br J Dermatol. 2007;157:165–7.

    Article  CAS  PubMed  Google Scholar 

  38. Gostout BS, Poland GA, Calhoun ES, et al. TAP1, TAP2, and HLA-DR2 alleles are predictors of cervical cancer risk. Gynecol Oncol. 2003;88:326–32.

    Article  CAS  PubMed  Google Scholar 

  39. Fong CL, Siddiqui AH, Mark DF. Identification and characterization of a novel repressor site in the human tumor necrosis factor alpha gene. Nucleic Acids Res. 1994;22:1108–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. kaluza W, Reuss E, Grossmann S, et al. Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism. J Invest Dermatol. 2000;114:1180–3.

    Article  CAS  PubMed  Google Scholar 

  41. Matsumoto K, Oki A, Satoh T, et al. Interleukin-10–1082 gene polymorphism and susceptibility to cervical cancer among Japanese women. Jpn J Clin Oncol. 2010;40:1113–6.

    Article  PubMed  Google Scholar 

  42. Zoodsma M, Nolte IM, Schipper M, et al. Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease. Int J Gynecol Cancer. 2005;15:282–90.

    Article  PubMed  Google Scholar 

  43. Govan VA, Carrara HR, Sachs JA, Hoffman M, Stanczuk GA, Williamson AL. Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer. J Carcinog. 2003;2:3.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Szöke K, Szalmás A, Szládek G, et al. IL-10 promoter nt -1082A/G polymorphism and human papillomavirus infection in cytologic abnormalities of the uterine cervix. J Interferon Cytokine Res. 2004;24:245–51.

    Article  PubMed  Google Scholar 

  45. Reynard MP, Turner D, Navarrete CV. Allele frequencies of polymorphisms of the tumour necrosis factor-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenet. 2000;27:241–9.

    Article  CAS  PubMed  Google Scholar 

  46. Perrey C, Pravica V, Sinnott PJ, Hutchinson IV. Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factor-alpha genes: a technical report. Transpl Immunol. 1998;6:193–7.

    Article  CAS  PubMed  Google Scholar 

  47. Mok CC, Lanchbury JS, Chan DW, Lau CS. Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum. 1998;41:1090–5.

    Article  CAS  PubMed  Google Scholar 

  48. Poli F, Nocco A, Berra S, et al. Allele frequencies of polymorphisms of TNFA, IL-6, IL-10 and IFNG in an Italian Caucasian population. Eur J Immunogenet. 2002;29:237–40.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. IGEVET (Instituto de Genética Veterinaria “Ingeniero Fernando Noel Dulout”), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Calle 60 y 118 s/n, 1900, La Plata, Buenos Aires, Argentina

    Gisela Barbisan, Luis Orlando Pérez, Anahí Contreras & Carlos Daniel Golijow

Authors
  1. Gisela Barbisan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luis Orlando Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anahí Contreras
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlos Daniel Golijow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gisela Barbisan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barbisan, G., Pérez, L.O., Contreras, A. et al. TNF-α and IL-10 promoter polymorphisms, HPV infection, and cervical cancer risk. Tumor Biol. 33, 1549–1556 (2012). https://doi.org/10.1007/s13277-012-0408-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0408-1

Keywords

Search

Navigation