Wei Wen-Jun, Lu Zhong-Wu, Wang Yu, Zhu Yong-Xue, Wang Yu-Long, Ji Qing-Hai
Department of Head & Neck Surgery, Cancer Hospital, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Head & Neck Surgery, Cancer Hospital, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Cancer Genet. 2015 Mar;208(3):68-75. doi: 10.1016/j.cancergen.2015.01.004. Epub 2015 Jan 30.
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.
在两项全基因组关联研究（GWAS）中，已报告有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的临床意义仍不明确。在一项病例对照研究中，对来自中国汉族人群的838例甲状腺乳头状癌（PTC）患者和501例良性甲状腺肿瘤（BTT）患者进行了基因分型，分析了四个GWAS鉴定出的PTC相关SNP，即rs965513、rs944289、rs966423和rs2439302。研究了这些SNP与PTC患者临床病理特征及预后之间的关联。rs966423的CT和CT + TT基因型在伴有甲状腺外侵犯和T分期更高的PTC患者中更为常见。rs944289的TC和TC + CC基因型以及C等位基因在多灶性疾病患者中的频率显著更低。短期随访后，未观察到GWAS鉴定出的SNP与PTC疾病持续存在之间存在相关性。在所有四个选定的SNP中，PTC组和BTT组之间的等位基因分布存在显著差异。与具有零个或1个风险等位基因的个体相比，具有超过五个风险等位基因的个体患PTC的可能性高8.84倍（95%CI 3.23 - 24.17）。GWAS鉴定出的SNP影响个体对PTC的易感性，且不与现有的桥本甲状腺炎和BTT病变相互作用。GWAS鉴定出的SNP与PTC的某些临床病理特征相关，可能有助于识别具有不同临床模式的PTC患者。需要进行大规模前瞻性研究以进一步评估这些基因标记物的诊断和预后能力。
