Common variants at 9q22.33, 14q13.3, and ATM loci, and risk of differentiated thyroid cancer in the French Polynesian population.
Common variants at 9q22.33, 14q13.3, and ATM loci, and risk of differentiated thyroid cancer in the French Polynesian population.
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DOI：
10.1371/journal.pone.0123700
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
de Vathaire F
中科院分区：
文献类型：
--
作者：
Maillard S;Damiola F;Clero E;Pertesi M;Robinot N;Rachédi F;Boissin JL;Sebbag J;Shan L;Bost-Bezeaud F;Petitdidier P;Doyon F;Xhaard C;Rubino C;Blanché H;Drozdovitch V;Lesueur F;de Vathaire F
法属波利尼西亚是世界上甲状腺癌发病率最高的国家之一。大气核武器试验与其他环境、生物或行为因素之间的关系已得到报告，但遗传易感性尚未得到调查。我们评估了GWAS鉴定的9q22.33和14q13.3位点以及DNA修复基因ATM内的多态性对177例和275例本地人群中分化性甲状腺癌（DTC）风险的贡献。对于FOXE1附近的GWAS SNP rs965513，发现基因型G/A和A/A与DTC风险之间存在关联。甚至还发现了等位基因A的倍增效应。携带FOXE1中多丙氨酸通道扩展的两个长等位基因的个体也观察到额外的风险，而在该基因的启动子区域未观察到与rs1867277下降的关联。相比之下，GWAS SNP rs944289 （NKX2-1）没有显示出任何显著的关联。虽然ATM错义替换D1853N （rs1801516）在人群中很少见，但携带小等位基因(A)的人也有过高的风险。这五种多态性与DTC风险之间的关系并不取决于体表面积、体重指数、种族或膳食碘摄入量。然而，甲状腺辐射剂量与rs944289之间存在相互作用。法属波利尼西亚的高发病率与所研究的多态性之间没有明确的联系，这些多态性涉及其他人群对DTC的易感性。与欧洲人群相比，在波利尼西亚人群中观察到等位基因频率的重要变化。对于FOXE1 rs965513，关联方向和效应大小与在其他人群中观察到的相似，而对于ATM rs1801516，次要等位基因与波利尼西亚人群的风险增加和欧洲人群的风险降低相关。
French Polynesia has one of the highest incidence rates of thyroid cancer worldwide. Relationships with the atmospheric nuclear weapons tests and other environmental, biological, or behavioral factors have already been reported, but genetic susceptibility has yet to be investigated. We assessed the contribution of polymorphisms at the 9q22.33 and 14q13.3 loci identified by GWAS, and within the DNA repair gene ATM, to the risk of differentiated thyroid cancer (DTC) in 177 cases and 275 matched controls from the native population. For the GWAS SNP rs965513 near FOXE1, an association was found between genotypes G/A and A/A, and risk of DTC. A multiplicative effect of allele A was even noted. An excess risk was also observed in individuals carrying two long alleles of the poly-alanine tract expansion in FOXE1, while no association was observed with rs1867277 falling in the promoter region of the gene. In contrast, the GWAS SNP rs944289 (NKX2-1) did not show any significant association. Although the missense substitution D1853N (rs1801516) in ATM was rare in the population, carriers of the minor allele (A) also showed an excess risk. The relationships between these five polymorphisms and the risk of DTC were not contingent on the body surface area, body mass index, ethnicity or dietary iodine intake. However, an interaction was evidenced between the thyroid radiation dose and rs944289. A clear link could not be established between the high incidence in French Polynesia and the studied polymorphisms, involved in susceptibility to DTC in other populations. Important variation in allele frequencies was observed in the Polynesian population as compared to the European populations. For FOXE1 rs965513, the direction of association and the effect size was similar to that observed in other populations, whereas for ATM rs1801516, the minor allele was associated to an increased risk in the Polynesian population and with a decreased risk in the European population.
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影响因子：
3.6
作者：
Edvardsen, Hege;Tefre, Toril;Jansen, Laila;Vu, Phuong;Haffty, Bruce G.;Fossa, Sophie D.;Kristensen, Vessela N.;Borresen-Dale, Anne-Lise
通讯作者：
Borresen-Dale, Anne-Lise
影响因子：
10.3
作者：
Cardis, E;Kesminiene, A;Williams, D
通讯作者：
Williams, D
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
30.8
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
通讯作者：
Stefansson, Kari
影响因子：
5.3
作者：
Carre, Aurore;Castanet, Mireille;Polak, Michel
通讯作者：
Polak, Michel