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中国人群中miR-149 Rs2292832多态性与甲状腺乳头状癌风险及临床病理特征的关联

Association of the miR-149 Rs2292832 polymorphism with papillary thyroid cancer risk and clinicopathologic characteristics in a Chinese population.

作者信息

Wei Wen-Jun, Lu Zhong-Wu, Li Duan-Shu, Wang Yu, Zhu Yong-Xue, Wang Zhuo-Ying, Wu Yi, Wang Yu-Long, Ji Qing-Hai

机构信息

Department of Head & Neck Surgery, Cancer Hospital, Fudan University, Shanghai 200032, China.

出版信息

Int J Mol Sci. 2014 Nov 14;15(11):20968-81. doi: 10.3390/ijms151120968.

Abstract

(1) BACKGROUND: The genetic predisposition to papillary thyroid cancer (PTC) is far from clearly elucidated. Rs2292832 is a genetic polymorphism that located in the precursor of mir-149 and has been studied in diverse cancers. Thus far, the role of rs2292832 in PTC tumorigenesis and progression was unclear; (2) METHOD: Rs2292832 was genotyped in 838 PTCs, 495 patients with thyroid benign tumors (BNs) and 1006 controls in a Chinese Han population. Clinicopathological data was collected and compared. The expression level of mature mir-149 was examined in 55 normal thyroid tissue samples; (3) RESULTS: The CC genotype of rs2292832 was significantly associated with an increased risk of PTC compared with TT homozygote (OR = 1.60, 95% CI: 1.72-2.20, p = 0.003) and TT/TC combined genotype (OR = 1.54, 95% CI: 1.14-2.09, p = 0.005). Rs2292832 is an independent risk factor correlated with tumor invasion (p = 0.006) and higher T stage in PTC patients (p = 0.007), but uncorrelated with short-term disease persistence of PTC. PTC subjects carrying CC genotype have lower mir-149-5p expression than those with TC genotype (p = 0.002). Twelve predicted target genes have been identified by collaboratively using computational tools; (4) CONCLUSION: Rs2292832 was possibly involved in the susceptibility and local progression of PTC in Chinese patients, by altering the expression level of mir-149-5p and its target genes.

摘要

(1) 背景:甲状腺乳头状癌(PTC)的遗传易感性远未明确阐明。Rs2292832是一种位于mir - 149前体的基因多态性,已在多种癌症中进行研究。迄今为止,Rs2292832在PTC肿瘤发生和进展中的作用尚不清楚;(2) 方法:对中国汉族人群中的838例PTC患者、495例甲状腺良性肿瘤(BN)患者和1006例对照进行Rs2292832基因分型。收集并比较临床病理数据。检测55例正常甲状腺组织样本中成熟mir - 149的表达水平;(3) 结果:与TT纯合子相比,Rs2292832的CC基因型与PTC风险增加显著相关(OR = 1.60,95%CI:1.72 - 2.20,p = 0.003),与TT/TC联合基因型相比也显著相关(OR = 1.54,95%CI:1.14 - 2.09,p = 0.005)。Rs2292832是与肿瘤侵袭(p = 0.006)和PTC患者较高T分期(p = 0.007)相关的独立危险因素,但与PTC的短期疾病持续时间无关。携带CC基因型的PTC受试者比携带TC基因型的受试者mir - 149 - 5p表达更低(p = 0.002)。通过联合使用计算工具已鉴定出12个预测的靶基因;(4) 结论:Rs2292832可能通过改变mir - 149 - 5p及其靶基因的表达水平参与中国患者PTC的易感性和局部进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7687/4264206/7e1c2effee24/ijms-15-20968-g001.jpg

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