The Common Genetic Variant rs944289 on Chromosome 14q13.3 Associates with Risk of Both Malignant and Benign Thyroid Tumors in the Japanese Population
The Common Genetic Variant rs944289 on Chromosome 14q13.3 Associates with Risk of Both Malignant and Benign Thyroid Tumors in the Japanese Population
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DOI：
10.1089/thy.2014.0431
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发表时间：
2015-03-01
期刊：
影响因子：
6.6
通讯作者：
Saenko, Vladimir A.
中科院分区：
文献类型：
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作者：
Rogounovitch, Tatiana I.;Bychkov, Andrey;Saenko, Vladimir A.
背景：一些单核苷酸多态性 (SNP) 已被确定与不同种族背景人群中分化型甲状腺癌的风险相关。这些遗传标记与甲状腺良性肿瘤滤泡腺瘤 (FA) 的关系尚未明确。方法：在一项多中心回顾性病例对照研究中，五个与甲状腺癌相关的 SNP-rs966513 (9q22.33, FOXE1)、rs944289 (14q13.3, PTCSC3)、 rs2439302 (8p12, NRG1)、rs1867277 (9q22.23, FOXE1) 和 rs6983267 (8q24, POU5F1B) 在 959 例经组织学验证的 FA、535 例甲状腺乳头状癌 (PTC) 和 2766 例人群对照中进行了基因分型。 结果： FA 与 rs944289 之间存在显着关联（p=0.002；OR 1.176 [CI 1.064-1.316]），并且与 rs2439302 显着相关（p=0.033；OR 1.149 [CI 1.010-1.315]）。在 PTC 中，确认了 rs965513 (p=4.21E-04；OR 1.587 [CI 1.235-2.000]) 和 rs944289 (p=0.003；OR 1.234 [CI 1.075-1.408]) 的显着关联，这是新发现的 rs2439302 (p=0.003；OR 1.266 [CI 1.087-1.493]）和 rs1867277（p=1.17E-04；OR 1.492 [CI 1.235-1.818]），并且在本系列中未针对 rs6983267（p=0.082；OR 1.136 [CI 0.980-1.316]）进行重复。在 PTC 的正常和肿瘤对应物中检测到 rs2439302 基因型与 NRG1 相对表达之间存在显着相关性（每个风险等位基因减少约 10%）。 NRG1 表达也与 PTCSC3 显着相关。结论：rs944289（之前已知会增加甲状腺癌风险）与 FA 的关联，以及 PTCSC3 和 NRG1 表达之间的相关性表明，诱发遗传因素在良性和恶性甲状腺肿瘤中部分常见，并意味着它们所涉及的途径具有更广泛的作用。 甲状腺肿瘤的发生，不仅限于癌变。
Background: Several single nucleotide polymorphisms (SNP) have been identified to be associated with the risk for differentiated thyroid cancer in populations of distinct ethnic background. The relationship of these genetic markers to a benign tumor of the thyroid, follicular adenoma (FA), is not well established.Methods: In a multicenter retrospective case-control study, five thyroid cancer-related SNPs-rs966513 (9q22.33, FOXE1), rs944289 (14q13.3, PTCSC3), rs2439302 (8p12, NRG1), rs1867277 (9q22.23, FOXE1), and rs6983267 (8q24, POU5F1B)-were genotyped in 959 cases of histologically verified FA, 535 papillary thyroid carcinomas (PTC), and 2766 population controls.Results: A significant association was found between FA and rs944289 (p=0.002; OR 1.176 [CI 1.064-1.316]), and suggestively with rs2439302 (p=0.033; OR 1.149 [CI 1.010-1.315]). In PTC, significant associations were confirmed for rs965513 (p=4.21E-04; OR 1.587 [CI 1.235-2.000]) and rs944289 (p=0.003; OR 1.234 [CI 1.075-1.408]), newly found for rs2439302 (p=0.003; OR 1.266 [CI 1.087-1.493]) and rs1867277 (p=1.17E-04; OR 1.492 [CI 1.235-1.818]), and was not replicated for rs6983267 (p=0.082; OR 1.136 [CI 0.980-1.316]) in this series. A significant correlation between rs2439302 genotype and relative expression of NRG1 was detected in normal and tumor counterparts of PTC (about 10% decrease per each risk allele). NRG1 expression also significantly correlated with that of PTCSC3.Conclusions: Association of rs944289, which was previously known to confer risk for thyroid cancer, with FA, and the correlation between PTCSC3 and NRG1 expression demonstrates that predisposing genetic factors are partly common for benign and malignant thyroid tumors, and imply broader roles of the pathways they underlie in thyroid tumorigenesis, not limited to carcinogenesis.