, Volume 43, Issue 1, pp 161–169 | Cite as

A missense polymorphism (rs11466653, Met326Thr) of toll-like receptor 10 (TLR10) is associated with tumor size of papillary thyroid carcinoma in the Korean population

  • Su Kang Kim
  • Hae Jeong Park
  • Il Ki Hong
  • Joo-Ho ChungEmail author
  • Young Gyu EunEmail author
Original Article


Toll-like receptors (TLRs) are important components of innate immune response. The aim of this study was to investigate whether TLR gene cluster (TLR10-TLR1-TLR6) polymorphisms are associated with the etiology of papillary thyroid carcinoma (PTC) and its clinicopathologic characteristics. We recruited 94 PTC patients and 325 control subjects. Genotypes for each SNP were determined by direct sequencing. SNPStats and SPSS 18.0 were used to evaluate odds ratios (ORs), 95 % confidence intervals (CIs), and P values. Multiple logistic regression analyzes of genetic data were performed. The missense SNP rs11466653 was associated with small tumor size (<1 cm) in PTC. The frequency of the rs11466653 T allele was higher in PTC patients with tumors <1 cm in size than in the control group (95.8 vs. 87.2 %; P = 0.021, OR = 0.30, 95 % CI = 0.11–0.83). The T allele of rs11466653 (T/C, Met326Thr) in TLR10 may be a risk factor for the development of tumors in PTC in the Korean population.


Toll-like receptor Papillary thyroid carcinoma Single nucleotide polymorphism Tumor size Association study 


Conflicts of interest

There are no potential conflicts of interest relevant to this study to report.


  1. 1.
    K.W. Jung, S. Park, H.J. Kong, Y.J. Won, J.Y. Lee, H.G. Seo, J.S. Lee, Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2009. Cancer Res. Treat. 44, 11–24 (2012)PubMedCrossRefGoogle Scholar
  2. 2.
    A.Y. Chen, A. Jemal, E.M. Ward, Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer 115, 3801–3807 (2009)PubMedCrossRefGoogle Scholar
  3. 3.
    A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, M.J. Thun, Cancer statistics, 2009. CA Cancer J. Clin. 59, 225–249 (2009)PubMedCrossRefGoogle Scholar
  4. 4.
    M.G. Borrello, L. Alberti, A. Fischer, D. Degl’innocenti, C. Ferrario, M. Gariboldi, F. Marchesi, P. Allavena, A. Greco, P. Collini, S. Pilotti, G. Cassinelli, P. Bressan, L. Fugazzola, A. Mantovani, M.A. Pierotti, Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc. Natl Acad. Sci. USA 102, 14825–14830 (2005)PubMedCrossRefGoogle Scholar
  5. 5.
    A. Pellegrini, N. Guinazu, L. Giordanengo, R.C. Cano, S. Gea, The role of toll-like receptors and adaptive immunity in the development of protective or pathological immune response triggered by the Trypanosoma cruzi protozoan. Future Microbiol. 6, 1521–1533 (2011)PubMedCrossRefGoogle Scholar
  6. 6.
    N. Dalgic, D. Tekin, Z. Kayaalti, T. Soylemezoglu, E. Cakir, B. Kilic, B. Kutlubay, M. Sancar, M. Odabasi, Arg753Gln polymorphism of the human toll-like receptor 2 gene from infection to disease in pediatric tuberculosis. Hum. Immunol. 72, 440–445 (2011)PubMedCrossRefGoogle Scholar
  7. 7.
    N.S. Palikhe, S.H. Kim, J.H. Kim, P. Losol, Y.M. Ye, H.S. Park, Role of toll-like receptor 3 variants in aspirin-exacerbated respiratory disease. Allergy Asthma Immunol. Res. 3, 123–127 (2011)PubMedCrossRefGoogle Scholar
  8. 8.
    M.L. Sales, R. Schreiber, M.C. Ferreira-Sae, M.N. Fernandes, C.S. Piveta, J.A. Cipolli, C.C. Cardoso, J.R. Matos-Souza, B. Geloneze, K.G. Franchini, W. Nadruz Jr, Toll-like receptor 6 Ser249Pro polymorphism is associated with lower left ventricular wall thickness and inflammatory response in hypertensive women. Am. J. Hypertens. 23, 649–654 (2010)PubMedCrossRefGoogle Scholar
  9. 9.
    F.A. Castro, A. Forsti, S. Buch, H. Kalthoff, C. Krauss, M. Bauer, J. Egberts, B. Schniewind, D.C. Broering, S. Schreiber, M. Schmitt, J. Hampe, K. Hemminki, C. Schafmayer, TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer. Eur. J. Cancer 47, 1203–1210 (2011)PubMedCrossRefGoogle Scholar
  10. 10.
    Z. Vidas, Polymorphisms in toll-like receptor genes—implications for prostate cancer development. Coll. Antropol. 34, 779–783 (2010)PubMedGoogle Scholar
  11. 11.
    U. Hasan, C. Chaffois, C. Gaillard, V. Saulnier, E. Merck, S. Tancredi, C. Guiet, F. Briere, J. Vlach, S. Lebecque, G. Trinchieri, E.E. Bates, Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J. Immunol. 174, 2942–2950 (2005)PubMedGoogle Scholar
  12. 12.
    T. Chuang, R.J. Ulevitch, Identification of hTLR10: a novel human toll-like receptor preferentially expressed in immune cells. Biochim. Biophys. Acta 1518, 157–161 (2001)PubMedCrossRefGoogle Scholar
  13. 13.
    R. Medzhitov, P. Preston-Hurlburt, C.A. Janeway Jr, A human homologue of the Drosophila toll protein signals activation of adaptive immunity. Nature 388, 394–397 (1997)PubMedCrossRefGoogle Scholar
  14. 14.
    X. Du, A. Poltorak, Y. Wei, B. Beutler, Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur. Cytokine Netw. 11, 362–371 (2000)PubMedGoogle Scholar
  15. 15.
    O. Takeuchi, T. Kawai, P.F. Muhlradt, M. Morr, J.D. Radolf, A. Zychlinsky, K. Takeda, S. Akira, Discrimination of bacterial lipoproteins by toll-like receptor 6. Int. Immunol. 13, 933–940 (2001)PubMedCrossRefGoogle Scholar
  16. 16.
    O. Takeuchi, S. Sato, T. Horiuchi, K. Hoshino, K. Takeda, Z. Dong, R.L. Modlin, S. Akira, Cutting edge: role of toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169, 10–14 (2002)PubMedGoogle Scholar
  17. 17.
    A. Ozinsky, D.M. Underhill, J.D. Fontenot, A.M. Hajjar, K.D. Smith, C.B. Wilson, L. Schroeder, A. Aderem, The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl Acad. Sci. USA 97, 13766–13771 (2000)PubMedCrossRefGoogle Scholar
  18. 18.
    S. Janssens, R. Beyaert, Role of toll-like receptors in pathogen recognition. Clin. Microbiol. Rev. 16, 637–646 (2003)PubMedCrossRefGoogle Scholar
  19. 19.
    S. Lindstrom, D.J. Hunter, H. Gronberg, P. Stattin, F. Wiklund, J. Xu, S.J. Chanock, R. Hayes, P. Kraft, Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies. Cancer Epidemiol. Biomarkers Prev. 19, 873–876 (2010)PubMedCrossRefGoogle Scholar
  20. 20.
    S.L. Zheng, K. Augustsson-Balter, B. Chang, M. Hedelin, L. Li, H.O. Adami, J. Bensen, G. Li, J.E. Johnasson, A.R. Turner, T.S. Adams, D.A. Meyers, W.B. Isaacs, J. Xu, H. Gronberg, Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the CAncer Prostate in Sweden Study. Cancer Res. 64, 2918–2922 (2004)PubMedCrossRefGoogle Scholar
  21. 21.
    J. Sun, F. Wiklund, S.L. Zheng, B. Chang, K. Balter, L. Li, J.E. Johansson, G. Li, H.O. Adami, W. Liu, A. Tolin, A.R. Turner, D.A. Meyers, W.B. Isaacs, J. Xu, H. Gronberg, Sequence variants in toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. J. Natl. Cancer Inst. 97, 525–532 (2005)PubMedCrossRefGoogle Scholar
  22. 22.
    M. Canadas Garre, M. Lopez de la Torre Casares, P. Becerra Massare, M.A. Lopez Nevot, J. Villar Del Moral, N. Munoz Perez, R. Vilchez Joya, R. Montes Ramirez, J.M. Llamas Elvira, BRAF(T1799A) mutation in the primary tumor as a marker of risk, recurrence, or persistence of papillary thyroid carcinoma. Endocrinol. Nutr. 58, 175–184 (2011)PubMedCrossRefGoogle Scholar
  23. 23.
    R. Iuliano, D. Palmieri, H. He, A. Iervolino, E. Borbone, P. Pallante, A. Cianflone, R. Nagy, H. Alder, G.A. Calin, F. Trapasso, C. Giordano, C.M. Croce, A. de la Chapelle, A. Fusco, Role of PTPRJ genotype in papillary thyroid carcinoma risk. Endocr. Relat. Cancer 17, 1001–1006 (2010)PubMedCrossRefGoogle Scholar
  24. 24.
    A. Salajegheh, R.A. Smith, K. Kasem, V. Gopalan, M.R. Nassiri, R. William, A.K. Lam, Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: potential markers for aggressive phenotypes. Eur. J. Surg. Oncol. 37, 93–99 (2011)PubMedCrossRefGoogle Scholar
  25. 25.
    N. Kurtulmus, M. Duren, U. Ince, M. Cengiz Yakicier, O. Peker, O. Aydin, E. Altiok, S. Giray, H. Azizlerli, BRAF(V600E) mutation in Turkish patients with papillary thyroid cancer: strong correlation with indicators of tumor aggressiveness. Endocrine 42, 404–410 (2012)Google Scholar
  26. 26.
    M.P. Purdue et al., A pooled investigation of toll-like receptor gene variants and risk of non-Hodgkin lymphoma. Carcinogenesis 30, 275–281 (2009)PubMedCrossRefGoogle Scholar
  27. 27.
    V.L. Stevens, A.W. Hsing, J.T. Talbot, S.L. Zheng, J. Sun, J. Chen, M.J. Thun, J. Xu, E.E. Calle, C. Rodriguez, Genetic variation in the toll-like receptor gene cluster (TLR10-TLR1-TLR6) and prostate cancer risk. Int. J. Cancer 123, 2644–2650 (2008)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Kohwang Medical Research Institute, School of MedicineKyung Hee UniversitySeoulKorea
  2. 2.Nuclear Medicine, School of MedicineKyung Hee UniversitySeoulKorea
  3. 3.Department of Otolaryngology-Head and Neck Surgery, School of MedicineKyung Hee UniversitySeoulKorea

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