Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation
Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation
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DOI：
10.1002/ijc.28483
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发表时间：
2014-04-01
影响因子：
6.4
通讯作者：
Kesminiene, Ausrele
中科院分区：
文献类型：
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作者：
Damiola, Francesca;Byrnes, Graham;Kesminiene, Ausrele
儿童时期暴露于切尔诺贝利核事故的电离辐射后，甲状腺乳头状癌（PTC）的发病率急剧增加，被描述为有史以来发生的单一原因导致的一种类型肿瘤数量最多的。个体间对辐射反应的差异已被记录，并且遗传学在散发性 PTC 中的作用已得到充分证实，这表明遗传因素也可能影响辐射相关 PTC 的风险。为了研究环境和宿主因素如何相互作用来改变 PTC 风险，我们对 83 个病例和 324 个匹配对照样本进行了基因分型，这些对照样本取自生活在切尔诺贝利核电站事故放射性尘埃污染地区的儿童，发现了 19 种先前与 PTC、甲状腺生物学或辐射诱发的第二原发性肿瘤相关的多态性。发现 ATM 中的 rs1801516 (D1853N)（比值比 (OR) = 0.34，95% 置信区间 (CI) 0.16，0.73）和 FOXE1 启动子区域中的 rs1867277（OR = 1.55，95% CI 1.03，2.34）与 PTC 显着相关。其他多态性分析证实了这两个基因与 PTC 之间的关联。我们的研究结果表明，DNA双链断裂修复途径和甲状腺形态发生途径或甲状腺分化状态维持失调都与PTC的病因有关，并且所研究的基因多态性和辐射剂量似乎是PTC的独立倍增危险因素。暴露于切尔诺贝利核事故电离辐射的儿童患甲状腺乳头状癌（PTC）的病例急剧增加。在这项遗传风险因素研究中，作者发现 ATM 和 FOXE1 基因中的单核苷酸多态性 (SNP) 与暴露于辐射的儿童的 PTC 之间存在显着相关性。结果表明，PTC 的病因可能涉及 DNA 修复途径、甲状腺形态发生途径和/或甲状腺分化状态失调。
A dramatic increase in the incidence of papillary thyroid carcinoma (PTC) after childhood exposure to ionizing radiation from the Chernobyl nuclear accident has been described as the largest number of tumors of one type due to one cause that have ever occurred. inter-individual variations in response to radiation have been documented and the role of genetics in sporadic PTC is well established, suggesting that genetic factors may also affect the risk of radiation-related PTC. To investigate how environmental and host factors interplay to modify PTC risk, we genotyped 83 cases and 324 matched controls sampled from children living in the area contaminated by fallout from the Chernobyl power plant accident for 19 polymorphisms previously associated with PTC, thyroid biology or radiation-induced second primary tumors. Significant association with PTC was found for rs1801516 (D1853N) in ATM (odds ratio (OR) = 0.34, 95% confidence interval (CI) 0.16, 0.73) and rs1867277 in the promoter region of FOXE1 (OR = 1.55, 95% CI 1.03, 2.34). Analysis of additional polymorphisms confirmed the association between these two genes and PTC. Our findings suggest that both DNA double-strand break repair pathway and thyroid morphogenesis pathway or dysregulation of thyroid differentiated state maintenance are involved in the etiology of PTC, and that the studied genetic polymorphisms and radiation dose appear to act as independent multiplicative risk factors for PTC.What's new? Children who were exposed to ionizing radiation from the Chernobyl nuclear accident suffered a dramatic rise in cases of papillary thyroid carcinoma (PTC). In this study of genetic risk factors, the authors found a significant correlation between single nucleotide polymorphisms (SNPs) in ATM and FOXE1 genes and PTC in children exposed to the radiation. The results suggest that the aetiology of PTC may involve a DNA repair pathway, a thyroid morphogenesis pathway, and/or dysregulation of the differentiated state in the thyroid.