Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.
Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.
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DOI：
10.1038/ng.339
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发表时间：
2009-04
期刊：
影响因子：
30.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Gudmundsson, Julius;Sulem, Patrick;Gudbjartsson, Daniel F.;Jonasson, Jon G.;Sigurdsson, Asgeir;Bergthorsson, Jon T.;He, Huiling;Blondal, Thorarinn;Geller, Frank;Jakobsdottir, Margret;Magnusdottir, Droplaug N.;Matthiasdottir, Sigurborg;Stacey, Simon N.;Skarphedinsson, Oskar B.;Helgadottir, Hafdis;Li, Wei;Nagy, Rebecca;Aguillo, Esperanza;Faure, Eduardo;Prats, Enrique;Saez, Berta;Martinez, Mariano;Eyjolfsson, Gudmundur I.;Bjornsdottir, Unnur S.;Holm, Hilma;Kristjansson, Kristleifur;Frigge, Michael L.;Kristvinsson, Hoskuldur;Gulcher, Jeffrey R.;Jonsson, Thorvaldur;Rafnar, Thorunn;Hjartarsson, Hannes;Mayordomo, Jose I.;de la Chapelle, Albert;Hrafnkelsson, Jon;Thorsteinsdottir, Unnur;Kong, Augustine;Stefansson, Kari
为了寻找赋予甲状腺癌风险的序列变异，我们分别对192例和37，196例冰岛病例和对照进行了全基因组关联研究，然后对欧洲血统的个体进行了复制研究。在这里，我们发现位于9q22.33和14q13.3的两个常见变异与该疾病相关。总体而言，在9q22.33（OR = 1.75; P = 1.7 × 10−27）和14q13.3（OR = 1.37; P = 2.0 × 10−9）上观察到rs 965513和rs 944289的最强关联信号。与9q22.33位点最近的基因是FOXE 1（TTF 2），NKX 2 -1（TTF 1）是位于14q13.3位点的基因之一。这两种变异都有助于增加乳头状和滤泡性甲状腺癌的风险。大约3.7%的个体是两种变异的纯合子，他们患甲状腺癌的估计风险是非携带者的5.7倍。在一项对来自普通人群的大样本集的研究中，两个风险等位基因均与低浓度的促甲状腺激素（TSH）相关，9q22.33等位基因与低浓度的甲状腺素（T4）和高浓度的三碘甲状腺原氨酸（T3）相关。
In order to search for sequence variants conferring risk of thyroid cancer we conducted a genome-wide association study in 192 and 37,196 Icelandic cases and controls, respectively, followed by a replication study in individuals of European descent. Here we show that two common variants, located on 9q22.33 and 14q13.3, are associated with the disease. Overall, the strongest association signals were observed for rs965513 on 9q22.33 (OR = 1.75; P = 1.7 × 10−27) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 × 10−9). The gene nearest to the 9q22.33 locus is FOXE1 (TTF2) and NKX2-1 (TTF1) is among the genes located at the 14q13.3 locus. Both variants contribute to an increased risk of both papillary and follicular thyroid cancer. Approximately 3.7% of individuals are homozygous for both variants, and their estimated risk of thyroid cancer is 5.7-fold greater than that of noncarriers. In a study on a large sample set from the general population, both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH), and the 9q22.33 allele is associated with low concentration of thyroxin (T4) and high concentration of triiodothyronine (T3).
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影响因子：
2.5
作者：
Delellis, Ronald A.
通讯作者：
Delellis, Ronald A.
影响因子：
6.4
作者：
Czene, K;Lichtenstein, P;Hemminki, K
通讯作者：
Hemminki, K
DOI：
10.1073/pnas.0812591106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Jazdzewski, Krystian;Liyanarachchi, Sandya;De la Chapelle, Albert
通讯作者：
De la Chapelle, Albert
DOI：
10.1073/pnas.0802682105
发表时间：
2008-05-20
影响因子：
11.1
作者：
Jazdzewski, Krystian;Murray, Elizabeth L.;de la Chapelle, Albert
通讯作者：
de la Chapelle, Albert
影响因子：
6.2
作者：
Kebebew, E;Greenspan, FS;McMillan, A
通讯作者：
McMillan, A