J Korean Med Sci.  2012 Nov;27(11):1333-1338. 10.3346/jkms.2012.27.11.1333.

Association of Toll-Like Receptor 2 Polymorphisms with Papillary Thyroid Cancer and Clinicopathologic Features in a Korean Population

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Kyung Hee University School of Medicine, Seoul, Korea.
  • 2Kohwang Medical Research Institute, Kyung Hee University School of Medicine, Seoul, Korea. shdwer@khu.ac.kr
  • 3Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Seoul, Korea.
  • 4Department of Otorhinolaryngology-Head and Neck Surgery, Ilsong Memorial Institute of Head and Neck Cancer, Hallym University College of Medicine, Anyang, Korea.
  • 5Department of Oriental Physiology, Kyung Hee University College of Pharmacy, Seoul, Korea.

Abstract

Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) were analyzed in patients with papillary thyroid cancer (PTC; n = 133) and their clinicopathologic features and age-matched controls (n = 321) using direct sequencing. PTC patients were divided into subgroups according to size, number, location, extrathyroidal invasion and lymph node metastasis. The two SNPs of TLR2 gene were not associated with the development of PTC. In clinical analysis, two SNPs were associated with location of cancer (rs3804099, P = 0.032, OR, 0.52; 95% CI, 0.28-0.96 in log-additive model; rs3804100, P = 0.039, OR, 0.46, 95% CI, 0.22-0.96 in codominant1 model; P = 0.018, OR, 0.42, 95% CI, 0.21-0.87 in dominant model; P = 0.011, OR, 0.46, 95% CI, 0.25-0.85 in log-additive model). The allele frequencies of two SNPs also showed significant associations with location of cancer (rs3804099, P = 0.046, OR, 0.57, 95% CI, 0.33-0.99 and rs3804100, P = 0.019, OR = 0.52, 95% CI = 0.30-0.90). However, two SNPs were not associated with the clinicopathologic features of PTC. It is suggested that TLR2 polymorphisms may contribute to the clinicopathologic features of PTC, especially the PTC in both lobes.

Keyword

Papillary Thyroid Cancer; Single Nucleotide Polymorphisms; Clinicopathologic Characteristics; Toll-Like Receptors

MeSH Terms

Adult
Aged
Alleles
Asian Continental Ancestry Group/*genetics
Carcinoma/genetics/*pathology
Female
Gene Frequency
Genotype
Humans
Linkage Disequilibrium
Lymphatic Metastasis
Male
Middle Aged
Odds Ratio
*Polymorphism, Single Nucleotide
Republic of Korea
Thyroid Neoplasms/genetics/*pathology
Toll-Like Receptor 2/*genetics
Toll-Like Receptor 2

Reference

1. Knostman KA, Jhiang SM, Capen CC. Genetic alterations in thyroid cancer: the role of mouse models. Vet Pathol. 2007. 44:1–14.
2. Roses RE, Xu M, Koski GK, Czerniecki BJ. Radiation therapy and Toll-like receptor signaling: implications for the treatment of cancer. Oncogene. 2008. 27:200–207.
3. Ishihara H, Tanaka I, Nemoto K, Tsuneoka K, Cheeramakara C, Yoshida K, Ohtsu H. Immediate-early, transient induction of the interleukin-1 beta gene in mouse spleen macrophages by ionizing radiation. J Radiat Res. 1995. 36:112–124.
4. Hallahan DE, Spriggs DR, Beckett MA, Kufe DW, Weichselbaum RR. Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation. Proc Natl Acad Sci U S A. 1989. 86:10104–10107.
5. Nemoto K, Ishihara H, Tanaka I, Suzuki G, Tsuneoka K, Yoshida K, Ohtsu H. Expression of IL-1 beta mRNA in mice after whole body X-irradiation. J Radiat Res. 1995. 36:125–133.
6. McBride WH, Chiang CS, Olson JL, Wang CC, Hong JH, Pajonk F, Dougherty GJ, Iwamoto KS, Pervan M, Liao YP. A sense of danger from radiation. Radiat Res. 2004. 162:1–19.
7. Repplinger D, Bargren A, Zhang YW, Adler JT, Haymart M, Chen H. Is Hashimoto's thyroiditis a risk factor for papillary thyroid cancer? J Surg Res. 2008. 150:49–52.
8. Malchoff CD, Malchoff DM. Familial nonmedullary thyroid carcinoma. Cancer Control. 2006. 13:106–110.
9. Sturgis EM, Li G. Molecular epidemiology of papillary thyroid cancer: in search of common genetic associations. Thyroid. 2009. 19:1031–1034.
10. Elisei R, Romei C, Vorontsova T, Cosci B, Veremeychik V, Kuchinskaya E, Basolo F, Demidchik EP, Miccoli P, Pinchera A, et al. RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults. J Clin Endocrinol Metab. 2001. 86:3211–3216.
11. Ciampi R, Knauf JA, Kerler R, Gandhi M, Zhu Z, Nikiforova MN, Rabes HM, Fagin JA, Nikiforov YE. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J Clin Invest. 2005. 115:94–101.
12. Lizis-Kolus K, Kowalska A, Kozak-Klonowska B, Siolek M, Sluszniak J, Lubinski J, Cybulski C. Case report of a woman with monoclonal gammapathy and papillary thyroid carcinoma, diagnosed because of detection of CHEK2 (I157T) mutation in genetic examinations. Endokrynol Pol. 2010. 61:502–506.
13. Shifrin AL, Ogilvie JB, Stang MT, Fay AM, Kuo YH, Matulewicz T, Xenachis CZ, Vernick JJ. Single nucleotide polymorphisms act as modifiers and correlate with the development of medullary and simultaneous medullary/papillary thyroid carcinomas in 2 large, non-related families with the RET V804M proto-oncogene mutation. Surgery. 2010. 148:1274–1280.
14. Siraj AK, Al-Rasheed M, Ibrahim M, Siddiqui K, Al-Dayel F, Al-Sanea O, Uddin S, Al-Kuraya K. RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population. J Endocrinol Invest. 2008. 31:893–899.
15. Salajegheh A, Smith RA, Kasem K, Gopalan V, Nassiri MR, William R, Lam AK. Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: potential markers for aggressive phenotypes. Eur J Surg Oncol. 2011. 37:93–99.
16. Macagno A, Napolitani G, Lanzavecchia A, Sallusto F. Duration, combination and timing: the signal integration model of dendritic cell activation. Trends Immunol. 2007. 28:227–233.
17. Xu S, Koski GK, Faries M, Bedrosian I, Mick R, Maeurer M, Cheever MA, Cohen PA, Czerniecki BJ. Rapid high efficiency sensitization of CD8+ T cells to tumor antigens by dendritic cells leads to enhanced functional avidity and direct tumor recognition through an IL-12-dependent mechanism. J Immunol. 2003. 171:2251–2261.
18. Sato M, Kawagoe T, Meguro A, Ota M, Katsuyama Y, Ishihara M, Namba K, Kitaichi N, Morimoto S, Kaburaki T, et al. Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population. Mol Vis. 2011. 17:731–736.
19. Chen KH, Gu W, Zeng L, Jiang DP, Zhang LY, Zhou J, Du DY, Hu P, Liu Q, Huang SN, et al. Identification of haplotype tag SNPs within the entire TLR2 gene and their clinical relevance in patients with major trauma. Shock. 2011. 35:35–41.
20. Junpee A, Tencomnao T, Sanprasert V, Nuchprayoon S. Association between Toll-like receptor 2 (TLR2) polymorphisms and asymptomatic bancroftian filariasis. Parasitol Res. 2010. 107:807–816.
21. Davoodi H, Seow HF. Variant Toll-Like Receptor4 (Asp299Gly and Thr399Ile Alleles) and Toll-Like Receptor2 (Arg753Gln and Arg677Trp Alleles) in colorectal cancer. Iran J Allergy Asthma Immunol. 2011. 10:91–99.
22. Boraska Jelavić T, Barisic M, Drmić-Hofman I, Boraska V, Vrdoljak E, Peruzovic M, Hozo I, Puljiz Z, Terzic J. Microsatelite GT polymorphism in the toll-like receptor 2 is associated with colorectal cancer. Clin Genet. 2006. 70:156–160.
23. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009. 19:1167–1214.
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