Genome-Wide Association Study on Differentiated Thyroid Cancer
Genome-Wide Association Study on Differentiated Thyroid Cancer
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DOI：
10.1210/jc.2013-1941
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发表时间：
2013-10-01
影响因子：
5.8
通讯作者：
Forsti, Asta
中科院分区：
文献类型：
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作者：
Kohler, Aleksandra;Chen, Bowang;Forsti, Asta
背景：分化型甲状腺癌(DTC)的全基因组关联研究(GWASs)已确定与2q35(DIRC3)、8p12(NRG1)、9q22.33(FOXE1)和14q13.2(NKX2-1)的多态有关。设计：我们对690例DTC高发人群和497名对照人群进行了遗传相关分析，并对2个意大利高发人群和3个低发人群共2958例和3727名对照人群进行了最显著的基因多态追踪。结果：在排除了先前发现的最重要的基因座(9q22.33)后，rs6759952显示了最强的关联，证实了最近发表在DIRC3中的关联(优势比[OR]=1.21，P=6.4 x 10(-10)，GWAS和所有复制的总和)。此外，在意大利序列的联合分析中，IMMP2L中的rs10238549和rs7800391(OR=1.27，P=4.1×10(-6)；OR=1.25，P=5.7×10(-6))，RARRES1中的rs7617304(OR=1.25，P=4.6×10(-5))和SNAPC4/CARD9中的rs10781500(OR=1.23，P=3.5×10(-5))与提示关联。还需要更多的研究来确定已识别的基因多态性在DTC发生中的作用以及它们在临床实践中的可能用途。
Context: Genome-wide association studies(GWASs) of differentiated thyroid cancer (DTC) have identified associations with polymorphisms at 2q35 (DIRC3), 8p12 (NRG1), 9q22.33 (FOXE1), and 14q13.2 (NKX2-1). However, most of the inherited genetic risk factors of DTC remain to be discovered.Objective: Our objective was to identify additional common DTC susceptibility loci.Design: We conducted a GWAS in a high-incidence Italian population of 690 cases and 497 controls and followed up the most significant polymorphisms in 2 additional Italian series and in 3 low-incidence populations totaling 2958 cases and 3727 controls.Results: After excluding the most robust previously identified locus (9q22.33), the strongest association was shown by rs6759952, confirming the recently published association in DIRC3 (odds ratio [OR] = 1.21, P = 6.4 x 10(-10), GWAS and all replications combined). Additionally, in the combined analysis of the Italian series, suggestive associations were attained with rs10238549 and rs7800391 in IMMP2L (OR = 1.27, P = 4.1 x 10(-6); and OR = 1.25, P = 5.7 x 10(-6)), rs7617304 in RARRES1 (OR = 1.25, P = 4.6 x 10(-5)) and rs10781500 in SNAPC4/CARD9 (OR = 1.23, P = 3.5 x 10(-5)).Conclusions: Our findings provide additional insights into the genetic and biological basis of inherited genetic susceptibility to DTC. Additional studies are needed to determine the role of the identified polymorphisms in the development of DTC and their possible use in the clinical practice.