Clinical significance of papillary thyroid cancer risk loci identified by genome-wide association studies
Clinical significance of papillary thyroid cancer risk loci identified by genome-wide association studies
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全基因组关联研究确定的乳头状甲状腺癌风险位点的临床意义。
DOI：
10.1016/j.cancergen.2015.01.004
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发表时间：
2015-03-01
期刊：
影响因子：
1.9
通讯作者：
Ji, Qing-Hai
中科院分区：
文献类型：
--
作者：
Wei, Wen-Jun;Lu, Zhong-Wu;Ji, Qing-Hai
在两项全基因组关联研究（GWAS）中，四个单核苷酸多态性（SNP）与甲状腺癌风险相关，并在中国人群中得到验证。由于缺乏进一步的临床和功能证据，这些SNP的临床意义仍然未知。在838例甲状腺乳头状癌（PTC）患者和501例良性甲状腺肿瘤（BTT）患者的病例对照研究中，对GWAS鉴定的4个PTC单核苷酸多态性（rs 965513、rs 944289、rs 966423和rs 2439302）进行基因分型。这些SNPs，临床病理特征，PTC患者的结果之间的关联进行了检查。rs 966423的CT和CT + TT基因型在甲状腺外浸润和T分期较晚的PTC患者中更常见。TC和TC + CC基因型和rs 944289的C等位基因在多灶性疾病患者中的频率显著降低。在短期随访后，GWAS鉴定的SNP与PTC的疾病持续性之间没有观察到相关性。PTC和BTT组之间的显着不同的等位基因分布观察到所有四个选定的SNP。携带5个以上危险等位基因的个体患PTC的可能性是携带0个或1个危险等位基因的个体的8.84倍（95% CI 3.23-24.17）。GWAS鉴定的SNPs影响PTC的个体易感性，而不与现有的桥本甲状腺炎和BTT病变相互作用。GWAS鉴定的SNPs与PTC的某些临床病理特征相关，可能有助于鉴别具有不同临床模式的PTC患者。需要进行大规模的前瞻性研究，以进一步评估这些遗传标记的诊断和预后能力。
Four single nucleotide polymorphisms (SNPs) have been reported to be associated with thyroid cancer risk in two genome-wide association studies (GWASs) and were validated in a Chinese population. Because of a lack of further clinical and functional evidence, the clinical significances of these SNPs remain unknown. Four GWAS-identified SNPs of papillary thyroid cancer (PTC), rs965513, rs944289, rs966423 and rs2439302, were genotyped in a case-control study of 838 patients with PTC and 501 patients with benign thyroid tumor (BTT) from the Chinese Han population. The associations between these SNPs, clinicopathologic features, and the outcome of the PTC patients were examined. The CT and CT + TT genotypes of rs966423 were more common in PTC patients with extrathyroidal extension and more advanced T stage. The TC and TC + CC genotypes and the C allele of rs944289 were significantly less frequent in patients with multifocal disease. No correlation was observed between GWAS-identified SNPs and disease persistence of PTC after a short-term follow-up. Significantly different allele distributions between the PTC and BTT groups were observed for all four selected SNPs. Individuals with more than five risk alleles were 8.84-fold (95% CI 3.23-24.17) more likely to suffer from PTC compared with those with zero or 1 risk allele. GWAS-identified SNPs affect the individual predisposition to PTC without interacting with existing Hashimoto thyroiditis and BTT lesions. GWAS-identified SNPs were associated with certain clinicopathologic features of PTC, and may contribute to identifying PTC patients with different clinical patterns. Large prospective studies are required to further evaluate the diagnostic and prognostic power of these genetic markers.