Zhanna Mussazhanova1,2, Tatiana I Rogounovitch3, Vladimir A Saenko4, Ainur Krykpayeva5, Maira Espenbetova5, Bauyrzhan Azizov6, Hisayoshi Kondo7, Katsuya Matsuda1, Zhanna Kalmatayeva2, Raushan Issayeva2, Zhanar Yeleubayeva2,8, Madina Madiyeva9, Aray Mukanova9, Marat Sandybayev10, Saltanat Bolsynbekova10, Zhanna Kozykenova11, Shunichi Yamashita3, Masahiro Nakashima1. 1. Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan. 2. Faculty of Medicine and Health Care, Al-Farabi Kazakh National University, Almaty, Kazakhstan. 3. Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan. 4. Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan. 5. Department of Endocrinology, Semey Medical University, Semey, Kazakhstan. 6. Endovascular Laboratory of Training Hospital, Semey Medical University, Semey, Kazakhstan. 7. Biostatics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan. 8. Center of Morphological Examination, Kazakh Institute of Oncology and Radiology, Almaty, Kazakhstan. 9. Radiology and Nuclear Medicine, Semey Medical University, Semey, Kazakhstan. 10. Center of Nuclear Medicine and Oncology of Semey, Semey, Kazakhstan. 11. Department of Pathological Physiology, Semey Medical University, Semey, Kazakhstan.
Abstract
Objective: Risk for developing papillary thyroid carcinoma (PTC), the most common endocrine malignancy, is thought to be mediated by lifestyle, environmental exposures and genetic factors. Recent progress in the genome-wide association studies of thyroid cancer leads to the identification of several genetic variants conferring risk to this malignancy across different ethnicities. We set out to elucidate the impact of selected single nucleotide polymorphisms (SNPs) on PTC risk and to evaluate clinicopathological correlations of these genetic variants in the Kazakh population for the first time. Methods: Eight SNPs were genotyped in 485 patients with PTC and 1,008 healthy control Kazakh subjects. The association analysis and multivariable modeling of PTC risk by the genetic factors, supplemented with rigorous statistical validation, were performed. Result: Five of the eight SNPs: rs965513 (FOXE1/PTCSC2, P = 1.3E-16), rs1867277 (FOXE1 5'UTR, P = 7.5E-06), rs2439302 (NRG1 intron 1, P = 4.0E-05), rs944289 (PTCSC3/NKX2-1, P = 4.5E-06) and rs10136427 (BATF upstream, P = 9.8E-03) were significantly associated with PTC. rs966423 (DIRC3, P = 0.07) showed a suggestive association. rs7267944 (DHX35) was associated with PTC risk in males (P = 0.02), rs1867277 (FOXE1) conferred the higher risk in subjects older than 55 years (P = 7.0E-05), and rs6983267 (POU5F1B/CCAT2) was associated with pT3-T4 tumors (P = 0.01). The contribution of genetic component (unidirectional independent effects of rs965513, rs944289, rs2439302 and rs10136427 adjusted for age and sex) to PTC risk in the analyzed series was estimated to be 30-40%. Conclusion: Genetic factors analyzed in the present work display significant association signals with PTC either on the whole group analysis or in particular clinicopathological groups and account for about one-third of the risk for PTC in the Kazakh population.
Objective: Risk for developing papillary thyroid carcinoma (PTC), the most common endocrine malignancy, is thought to be mediated by lifestyle, environmental exposures and genetic factors. Recent progress in the genome-wide association studies of thyroid cancer leads to the identification of several genetic variants conferring risk to this malignancy across different ethnicities. We set out to elucidate the impact of selected single nucleotide polymorphisms (SNPs) on PTC risk and to evaluate clinicopathological correlations of these genetic variants in the Kazakh population for the first time. Methods: Eight SNPs were genotyped in 485 patients with PTC and 1,008 healthy control Kazakh subjects. The association analysis and multivariable modeling of PTC risk by the genetic factors, supplemented with rigorous statistical validation, were performed. Result: Five of the eight SNPs: rs965513 (FOXE1/PTCSC2, P = 1.3E-16), rs1867277 (FOXE1 5'UTR, P = 7.5E-06), rs2439302 (NRG1 intron 1, P = 4.0E-05), rs944289 (PTCSC3/NKX2-1, P = 4.5E-06) and rs10136427 (BATF upstream, P = 9.8E-03) were significantly associated with PTC. rs966423 (DIRC3, P = 0.07) showed a suggestive association. rs7267944 (DHX35) was associated with PTC risk in males (P = 0.02), rs1867277 (FOXE1) conferred the higher risk in subjects older than 55 years (P = 7.0E-05), and rs6983267 (POU5F1B/CCAT2) was associated with pT3-T4 tumors (P = 0.01). The contribution of genetic component (unidirectional independent effects of rs965513, rs944289, rs2439302 and rs10136427 adjusted for age and sex) to PTC risk in the analyzed series was estimated to be 30-40%. Conclusion: Genetic factors analyzed in the present work display significant association signals with PTC either on the whole group analysis or in particular clinicopathological groups and account for about one-third of the risk for PTC in the Kazakh population.
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