Skip to main content
SpringerLink
Log in

Interleukin-10-1082 gene polymorphism is associated with papillary thyroid cancer

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The etiopathogenesis of thyroid cancer has not been clearly elucidated although the role of chronical inflammation and the imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with papillary thyroid cancer (PTC), and to evaluate the relationship between genotypes and clinical/laboratory manifestation of PTC. Tumor necrosis factorα (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 A-1082G (rs 1800896) single nucleotide polymorphisms in DNA from peripheral blood leukocytes of 190 patients with thyroid cancer and 216 healthy controls were investigated by real-time PCR combined with melting curve analysis. There was no notable risk for PTC afflicted by TNFα-308 and IL-6-174 alone. However, IL-10-1082 G allele frequency were higher among PTC patients than healthy controls (p = 0.009). The patients with IL-10-1082 GG geotype have twofold increased risk of developing thyroid cancer according to AA genotype (OR 2.07, 95 % CI 1.21–3.55). In addition, the concomitant presence of IL-10-1082 G allele (GG + AG genotypes) together with IL-6 -174 GG genotype has a nearly twofold increased risk for thyroid cancer (OR 1.75 with 95 % CI 1.00–3.05, p = 0.049). We suggest that IL-10-1082 G allele is associated with an increased risk of PTC. The polymorphism of IL-10 gene can improve our knowledge about the pathogenesis of PTC, and could provide to estimate people at the increased risk for PTC.

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. Khanafshar E, Lloyd RV (2011) The Spectrum of papillary thyroid carcinoma variants. Adv Anat Pathol 18:90–97

    Article  PubMed  Google Scholar 

  2. Lumashi F, Basso SMM, Orlando R (2010) Cytokines, thyroid diseases and thyroid cancer. Cytokine 50:229–233

    Article  Google Scholar 

  3. Shizuru JA (2001) Autoimmunitiy and endocrine diseases. In: Greenspan FS, Gardner DG (eds) Basic and clinical endocrinology. Lange Medical Books/McGraw-Hill, New York, pp 745–761

    Google Scholar 

  4. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Ajan RA, Watson PF, Weetman AP (1996) Cytokines and thyroid function. Adv Neuroimmunol 6:359–386

    Article  Google Scholar 

  6. de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JF (1991) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174:915–924

    Article  Google Scholar 

  7. Rousset F, Garcia T, Defrance T, Vezzio N, Peronne C, Hsu DH, Kastellein R, Moore KW, Banchereau J (1991) Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 89:1890–1893

    Article  Google Scholar 

  8. Mosmann TR (1994) Properties and functions of interleukin-10. Adv Immunol 56:1–10

    Article  CAS  PubMed  Google Scholar 

  9. Langsenlehner U, Krippl P, Renner W, Yazdani-Biuki B, Eder T, Köppel H, Wascher TC, Paulweber B, Samonigg H (2005) Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk. Breast Cancer Res Treat 90:113–115

    Article  CAS  PubMed  Google Scholar 

  10. Kubaszek A, Pihlajamaki J, Komarovski V, Lindi V, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Uusitupa M, Laakso M; Finnish Diabetes Prevention Study (2003) Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes 52:1872–1876

    Article  Google Scholar 

  11. Seifart C, Dempfle A, Plagens A, Seifart U, Clostermann U, Müller B, Vogelmeier C, von Wichert P (2005) TNF-α-, TNF-β-, IL-6-, and IL-10-promoter polymorphisms in patients with chronic obstructive pulmonary disease. Tissue Antigens 65:93–100

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Kroeger KM, Carville KS, Abraham LJ (1997) The −308 tumor necrosis factor-α promoter polymorphism effects transcription. Mol Immunol 34:391–399

    Article  CAS  PubMed  Google Scholar 

  14. Pereira DS, Garcia DM, Narciso FMS, Santos MLAS, Dias JMD, Queiroz B, Souza ER, Nobrega OT, Pereira LSM (2012) Effects of IL-6 G/C polymorphism in the promoter region of the interleukin-6 gene on plasma levels and muscle strength in elderly women. Braz J Med Biol Res 44:123–129

    Article  Google Scholar 

  15. Sen A, Paine SK, Chowdhury IH, Mukherjee A, Choudhuri S, Saha A, Mandal LK, Bhattacharaya B (2011) Impact of interleukin-6 promoter polymorphism and serum interleukin-6 level of acute inflammation and neovascularization stages of patients with Eales’ disease. Mol Vision 17:2552–2556

    CAS  Google Scholar 

  16. Belluco C, Olivieri F, Bonafe M, Giovagnetti S, Mammano E, Scalerta R, Ambrosi A, Franceschi C, Nitti D, Lise M (2003) −174 G > C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res 9:2173–2176

    CAS  PubMed  Google Scholar 

  17. Baki M, Akman FE, Vural P, Doğru-Abbasoğlu S, Özderya A, Karadağ B, Uysal M (2012) The combination of Interleukin-10-1082 and Tumor Necrosis Factorα-308 or Interleukin-6-174 genes polymorphisms suggests an association with susceptibility to Hashimoto’s thyroiditis. Int Immunopharmacol 12:543–546

    Article  CAS  PubMed  Google Scholar 

  18. Castro-Santos P, Suarez A, Lopez-Rivas L, Mozo L, Gutierrez C (2006) TNFα and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency. Am J Gastroenterol 101:1039–1047

    Article  CAS  PubMed  Google Scholar 

  19. Stonek F, Bentz EK, Hafner E, Metzenbauer M, Philipp K, Hefler LA, Tempfer CB (2007) A tumor necrosis factor-α promoter polymorphism and pregnancy complications: results of a prospective cohort study in 1652 pregnant women. Reprod Sci 14:425–429

    Article  CAS  PubMed  Google Scholar 

  20. Capurso C, Solfrizzi V, D’Introno A, Colacicco AM, Capurso SA, Capurso A, Panza F (2004) Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer’s disease: geographic allele and genotype variations in Europe. Exp Gerontol 39:1567–1573

    Article  CAS  PubMed  Google Scholar 

  21. Kissonergihs AM, Grubeck-Loebestein B, Feldmann M, Londei M (1989) Tumour necrosis factor synergises with gamma interferon on the induction of mRNA alpha chain on thyrocytes from Graves’ disease and nontoxic goitre. Autoimmunity 44:255–266

    Article  Google Scholar 

  22. Salvi M, Giarasole C, Pedrazzoni M, Passeri M, Giuliani N, Minelli R, Braverman LE, Roti E (1998) Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves’ disease. J Clin Endocrinol 81:2976–2979

    Google Scholar 

  23. Todaro M, Zerilli M, Ricci-Vitiani L, Bini M, Perez Alea M, Maria Florena A, Miceli L, Condorelli G, Bonventre S, Di Gesù G, De Maria R, Stassi G (2006) Autocrine production of interleukin-4 and interleukin-10 is required for survival and growth if thyroid cancer cells. Cancer Res 66:1491–1499

    Article  CAS  PubMed  Google Scholar 

  24. Chen RH, Chen WC, Wang TY, Tsai CH (2005) Lack of association between pto-inflammatory cytokine (IL-6, IL-8 and TNF-α) gene polymorphisms and Graves’ disease. Int J Immunogenet 32:343–347

    Article  CAS  PubMed  Google Scholar 

  25. Li M, You Q, Wang X (2011) Association between polymorphism of the tumor necrosis factor alpha-308 gene promoter and colon cancer in the Chinese population. Genet Test Mol Biomarkers 15:743–747

    Article  Google Scholar 

  26. Singh H, Jain M, Sachan R, Mittal B (2009) Association of TNFα (−308G > A) and IL-10 (819C > T) polymorphisms with the risk of cervical cancer. Int J Gynecol Cancer 19:1190–1194

    Article  PubMed  Google Scholar 

  27. Wei Y, Liu F, Li B, Chen X, Ma Y, Yan L, Wen T, Xu M, Wang W, Yang J (2011) Polymorphisms of tumor necrosisfactoralpha and hepatocellular carcinoma risk: a HuGE systematic review and meta-analysis. Dig Dis Sci 56(8):2227–2236

    Article  CAS  PubMed  Google Scholar 

  28. Correa GT, Bandeira GA, Calvacanti BG (2011) de Carvallo Fraga CA, dos Santos EP, Silva TF, Gomez RS, Guimaraes AL, De Paula AM. Oral Oncol 47:888–894

    Article  CAS  PubMed  Google Scholar 

  29. Sousa H, Breeda E, Santos AM, Catarino R, Pinto D, Medeiros R (2011) Genetic risk factors for nasolaryngeal carcinoma in Portugal: tomor necrosis factor alpha −308G > A polymorphism. DNA Cell Biol 30:99–103

    Article  CAS  PubMed  Google Scholar 

  30. Kesarwani P, Ahirwar DK, Mandhani A, Mittal RD (2008) Association between −174 G/C promoter polymorphism of the interleukin-6 gene and progression of prostate cancer in North Indian population. DNA Cell Biol 27:505–510

    Article  CAS  PubMed  Google Scholar 

  31. Ozgen AG, Karadeniz M, Erdogan M, Berdeli A, Saygili F, Yilmaz C (2009) The (−174) G/C polymorphism inthe iterleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish population. J Endocrinol Invest 32:491–494

    Article  CAS  PubMed  Google Scholar 

  32. Yu KD, Di GH, Fan L, Chen AX, Yang C, Shao SM (2010) Lack of association between functional polymorphisms in the interleukin-6 gene promoter and breast cancer risk: a meta-analysis involving 25703 subjects. Breast Cancer Res Treat 122:483–488

    Article  CAS  PubMed  Google Scholar 

  33. Aladzsty I, Kovacs M, Semsei A, Falus A, Szilagyi A, Karadi I, Varga G, Füst G, Varkonyi J (2009) Comparative analysis of IL-6 promoter and receptor polymorphisms im myelodysplasia and multiple myeloma. Leuk Res 33:1570–1573

    Article  Google Scholar 

  34. Eskale J, Kube D, Tesch H, Galagner G (1997) Mapping of the human IL-10 gene and further characterisation of the 5′flanking sequence. Immunogenetics 46:120–128

    Article  Google Scholar 

  35. Erdogan M, Karadeniz M, Ozbek M, Ozgen AG, Berdeli A (2008) Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population. J Endocrinol Invest 31:750–754

    Article  CAS  PubMed  Google Scholar 

  36. Cunha LL, Tincani AJ, da Assumpçao LVM, Soares FA, Vasallo J, Ward LS (2011) Interleukin-10 but not interleukin-18 may be associated with the immune response against well differentiated thyroid cancer. Clinics 66:1203–1208

    Article  PubMed Central  PubMed  Google Scholar 

  37. Peng WJ, He Q, Yang JX, Wang BX, Lu MM, Wang S, Wang J (2012) Meta-analysis of association between cytokine gene polymorphisms an lung cancer risk. Mol Biol Rep 39:5187–5194

    Article  CAS  PubMed  Google Scholar 

  38. Wang J, Ding Q, Shi Y, Cao Q, Qin C, Zhu J, Chen J, Yin C (2012) The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis. Mutagenesis 24:305–312

    Article  Google Scholar 

  39. Zhou Y, Hu W, Zhuang W, Wu X (2011) Interleukin-10-1082 promoter polymorphism and gastric cancer risk in Chinese Han population. Mol Cell Biochem 347:89–93

    Article  CAS  PubMed  Google Scholar 

  40. Shao N, Zu B, Mi YY, Hua LX (2011) IL-10 polymorphisms and prostate cancer risk: a meta-analysis. Prostate Cancer Prostatic Dis 14:129–135

    Article  CAS  PubMed  Google Scholar 

  41. Michaud DS, Daugherty SE, Berndt SI, Platz EA, Yeager M, Crawford ED, Hsing A, Huang WY, Hayes RB (2006) Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk of prostate cancer. Cancer Res 66:4525–4530

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Research Fund of Istanbul University Project No: 8763.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, Şişli Etfal Research and Training Hospital, Şişli, Istanbul, Turkey

    Esra Çil & Yüksel Altuntaş

  2. Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Çapa, Istanbul, 34093, Turkey

    Alkın Kumral, Müge Kanmaz-Özer, Pervin Vural, Semra Doğru-Abbasoğlu & Müjdat Uysal

Authors
  1. Esra Çil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alkın Kumral
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Müge Kanmaz-Özer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pervin Vural
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Semra Doğru-Abbasoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yüksel Altuntaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Müjdat Uysal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pervin Vural.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Çil, E., Kumral, A., Kanmaz-Özer, M. et al. Interleukin-10-1082 gene polymorphism is associated with papillary thyroid cancer. Mol Biol Rep 41, 3091–3097 (2014). https://doi.org/10.1007/s11033-014-3169-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3169-7

Keywords

Search

Navigation