SNP Association with Risk for Sporadic Papillary Thyroid Carcinoma in Kazakh Population

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Background: The recent genome-wide association studies (GWAS) including FOXE1 and NKX2-1 genes have represent associations for well differentiated thyroid carcinoma. Replication studies in geographically distinct populations identified strong associations of rs965513 (9q22.33) and rs944289 (14q13.3) SNPs with papillary thyroid cancer. This work is the first to characterise the associations of SNPs in a population-based Kazakh cohort.

Aims: To study association of SNPs with risk for sporadic papillary thyroid carcinoma (PTC) in Kazakh population.

Materials and methods: A total of 298 patients with histologically confirmed PTC and 742 controls of Kazakh origin were recruited. All participants donated a peripheral venous blood sample which was used to isolate genomic DNA. Genotyping was performed using TaqMan Genotyping on a Light Cycler 480 (Roche, Indianapolis, IN).

Results: Significant associations: rs965513 (p=3.24 E-16; OR=2.05, 95% CI 1.82−2.11) and rs944289 (p=1.38 E-06; OR=1.39, 95% CI 1.21−1.52) were found in the multiplicative model of inheritance adjusted for age and sex.

Conclusions: Our study unambiguously confirms the existence of genetic determinants of susceptibility to PTC in Kazakh population.

About the authors

Ainur S. Krykpayeva

Semey State Medical University

ORCID iD: 0000-0001-7701-9832



Masahiro Nakashima

Nagasaki University

ORCID iD: 0000-0002-9036-8735

MD, PhD, Professor


Maira Zh. Espenbetova

Semey State Medical University

ORCID iD: 0000-0003-2318-4765

MD, PhD, Professor


Zhanna Mussazhanova

Nagasaki University

Author for correspondence.
ORCID iD: 0000-0002-7315-7725

MD, PhD, AssistantProfessor.

852-8523, Sakamoto 1-12-4, Nagasaky


Baurzhan S. Azizov

Semey State Medical University

ORCID iD: 0000-0003-4775-8970




  1. Kweon SS, Shin MH, Chung IJ, et al. Thyroid cancer is the most common cancer in women, based on the data from population-based cancer registries, South Korea. Jpn J Clin Oncol. 2013;43(10):1039–1046. doi: 10.1093/jjco/hyt102.
  2. Kimura ET, Nikiforova MN, Zhu Z, et al. High prevalence of BRAF mutations in thyroid cancer. Cancer Res. 2003;63(7):1454–1457.
  3. Lloyd RV, Osamura RY, Klöppel G, Rosai J, editors. WHO Classification of Tumours of endocrine organs. WHO Classification of Tumours, 4th ed. Vol. 10. WHO; 2017. 355 p.
  4. Cardis E, Kesminiene A, Ivanov V, et al. Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst. 2005;97(10):724–732. doi: 10.1093/jnci/dji129.
  5. Takahashi M, Saenko VA, Rogounovitch TI, et al. The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl. Hum Mol Genet. 2010;19(12):2516–2523. doi: 10.1093/hmg/ddq123.
  6. Gudmundsson J, Sulem P, Gudbjartsson DF, et al. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat Genet. 2009;41(4):460–464. doi: 10.1038/ng.339.
  7. Matsuse M, Takahashi M, Mitsutake N, et al. 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. doi: 10.1136/jmedgenet-2011-100063.
  8. Pereda C, Lesueur F, Pertesi M, et al. Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population. BMC Genet. 2015;16:22. doi: 10.1186/s12863-015-0180-5.
  9. Penna-Martinez M, Epp F, Kahles H, et al. FOXE1 association with differentiated thyroid cancer and its progression. Thyroid. 2014;24(5):845–851. doi: 10.1089/thy.2013.0274.
  10. Jones AM, Howarth KM, Martin L, et al. Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24. J Med Genet. 2012;49(3):158–163. doi: 10.1136/jmedgenet-2011-100586.
  11. Guazzi S, Price M, De Felice M, et al. Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity. EMBO J. 1990;9(11):3631–3639. doi: 10.1002/j.1460-2075.1990.tb07574.x.
  12. Kendall J, Liu Q, Bakleh A, et al. Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer. Proc Natl Acad Sci U S A. 2007;104(42):16663–16668. doi: 10.1073/pnas.0708286104.
  13. Kimura S, Hara Y, Pineau T, et al. The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev. 1996;10(1):60–69. doi: 10.1101/gad.10.1.60.
  14. Li W, Ain KB. Human sodium–iodide symporter (hNIS) gene expression is inhibited by a trans-active transcriptional repressor, NIS-repressor, containing PARP-1 in thyroid cancer cells. Endocr Relat Cancer. 2010;17(2):383–398. doi: 10.1677/ERC-09-0156.
  15. Mitchell LE, Christensen K. Evaluation of family history data for Danish twins with nonsyndromic cleft lip with or without cleft palate. Am J Med Genet. 1997;72(1):120–121. doi: 10.1002/(sici)1096-8628(19971003)72:1<120::aid-ajmg25>;2-s.
  16. Tomaz RA, Sousa I, Silva JG, et al. FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility. Clin Endocrinol (Oxf). 2012;77(6):926–933. doi: 10.1111/j.1365-2265.2012.04505.x.
  17. Abramson JH. WINPEPI updated: computer programs for epidemiologists, and their teaching potential. Epidemiol Perspect Innov. 2011;8(1):1. doi: 10.1186/1742-5573-8-1.

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