Skip to main content
Log in

Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern China?

  • Research Article
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Papillary thyroid carcinoma (PTC) is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 (located at the 14q13.3 locus), which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained (C vs. T, P = 0.027, OR = 1.264, 95% CI = 1.026 - 1.557; and C/C - C/T vs. T/T, P = 0.034, OR = 1.474, 95% CI = 1.028 - 2.112). Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 (adjusted P = 0.062) between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction (P = 0.029; OR = 2.578, 95% CI = 1.104 - 6.023) between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Lang BH, Lo CY, Chan WF, Lam KY, Wan KY. Staging systems for papillary thyroid carcinoma: a review and comparison. Ann Surg 2007; 245(3): 366–378

    Article  PubMed Central  PubMed  Google Scholar 

  2. Czene K, Lichtenstein P, Hemminki K. Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer 2002; 99(2): 260–266

    Article  CAS  PubMed  Google Scholar 

  3. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006; 6(4): 292–306

    Article  CAS  PubMed  Google Scholar 

  4. DeLellis RA. Pathology and genetics of thyroid carcinoma. J Surg Oncol 2006; 94(8): 662–669

    Article  CAS  PubMed  Google Scholar 

  5. Meinhold CL, Ron E, Schonfeld SJ, Alexander BH, Freedman DM, Linet MS, Berrington de González A. Nonradiation risk factors for thyroid cancer in the US Radiologic Technologists Study. Am J Epidemiol 2010; 171(2): 242–252

    Article  PubMed Central  PubMed  Google Scholar 

  6. Leux C, Truong T, Petit C, Baron-Dubourdieu D, Guénel P. Family history of malignant and benign thyroid diseases and risk of thyroid cancer: a population-based case-control study in New Caledonia. Cancer Causes Control 2012; 23(5): 745–755

    Article  PubMed  Google Scholar 

  7. Shih SR, Chiu WY, Chang TC, Tseng CH. Diabetes and thyroid cancer risk: literature review. Exp Diabetes Res 2012; 2012: 578285

    Article  PubMed Central  PubMed  Google Scholar 

  8. Kimura S. Thyroid-specific transcription factors and their roles in thyroid cancer. J Thyroid Res 2011; 2011: 710213

    Article  PubMed Central  PubMed  Google Scholar 

  9. Katoh R, Kawaoi A, Miyagi E, Li X, Suzuki K, Nakamura Y, Kakudo K. Thyroid transcription factor-1 in normal, hyperplastic, and neoplastic follicular thyroid cells examined by immunohistochemistry and nonradioactive in situ hybridization. Mod Pathol 2000; 13(5): 570–576

    Article  CAS  PubMed  Google Scholar 

  10. Gudmundsson J, Sulem P, Gudbjartsson DF, Jonasson JG, Sigurdsson A, Bergthorsson JT, He H, Blondal T, Geller F, Jakobsdottir M, Magnusdottir DN, Matthiasdottir S, Stacey SN, Skarphedinsson OB, Helgadottir H, Li W, Nagy R, Aguillo E, Faure E, Prats E, Saez B, Martinez M, Eyjolfsson GI, Bjornsdottir US, Holm H, Kristjansson K, Frigge ML, Kristvinsson H, Gulcher JR, Jonsson T, Rafnar T, Hjartarsson H, Mayordomo JI, de la Chapelle A, Hrafnkelsson J, Thorsteinsdottir U, Kong A, Stefansson K. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat Genet 2009; 41(4): 460–464

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Matsuse M, Takahashi M, Mitsutake N, Nishihara E, Hirokawa M, Kawaguchi T, Rogounovitch T, Saenko V, Bychkov A, Suzuki K, Matsuo K, Tajima K, Miyauchi A, Yamada R, Matsuda F, Yamashita S. The FOXE1 and NKX2-1 loci are associated with susceptibility to papillary thyroid carcinoma in the Japanese population. J Med Genet 2011; 48(9): 645–648

    Article  CAS  PubMed  Google Scholar 

  12. Wang YL, Feng SH, Guo SC, Wei WJ, Li DS, Wang Y, Wang X, Wang ZY, Ma YY, Jin L, Ji QH, Wang JC. Confirmation of papillary thyroid cancer susceptibility loci identified by genomewide association studies of chromosomes 14q13, 9q22, 2q35 and 8p12 in a Chinese population. J Med Genet 2013; 50(10): 689–695

    Article  CAS  PubMed  Google Scholar 

  13. Tan D, Li Q, Deeb G, Ramnath N, Slocum HK, Brooks J, Cheney R, Wiseman S, Anderson T, Loewen G. Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study. Hum Pathol 2003; 34(6): 597–604

    Article  CAS  PubMed  Google Scholar 

  14. Moldvay J, Jackel M, Bogos K, Soltész I, Agócs L, Kovács G, Schaff Z. The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathol Oncol Res 2004; 10(2): 85–88

    Article  CAS  PubMed  Google Scholar 

  15. Hoshi S, Hoshi N, Okamoto M, Paiz J, Kusakabe T, Ward JM, Kimura S. Role of NKX2-1 in N-bis(2-hydroxypropyl)-nitrosamine-induced thyroid adenoma in mice. Carcinogenesis 2009; 30(9): 1614–1619

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Jendrzejewski J, He H, Radomska HS, Li W, Tomsic J, Liyanarachchi S, Davuluri RV, Nagy R, de la Chapelle A. The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type. Proc Natl Acad Sci USA 2012; 109(22): 8646–8651

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Fabbro D, Di Loreto C, Beltrami CA, Belfiore A, Di Lauro R, Damante G. Expression of thyroid-specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasms. Cancer Res 1994; 54(17): 4744–4749

    CAS  PubMed  Google Scholar 

  18. Ngan ES, Lang BH, Liu T, Shum CK, So MT, Lau DK, Leon TY, Cherny SS, Tsai SY, Lo CY, Khoo US, Tam PK, Garcia-Barceló MM. A germline mutation (A339V) in thyroid transcription factor-1 (TITF-1/NKX2.1) in patients with multinodular goiter and papillary thyroid carcinoma. J Natl Cancer Inst 2009; 101(3): 162–175

    CAS  Google Scholar 

  19. Sjakste T, Kalis M, Poudziunas I, Pirags V, Lazdins M, Groop L, Sjakste N. Association of microsatellite polymorphisms of the human 14q13.2 region with type 2 diabetes mellitus in Latvian and Finnish populations. Ann Hum Genet 2007; 71(6): 772–776

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qiong Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ai, L., Yu, Y., Liu, X. et al. Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern China?. Front. Med. 8, 113–117 (2014). https://doi.org/10.1007/s11684-014-0310-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-014-0310-x

Keywords

Navigation