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前体微小RNA-146a基因功能多态性对肾细胞癌风险及预后的影响

Effect of a functional polymorphism in the pre-miR-146a gene on the risk and prognosis of renal cell carcinoma.

作者信息

Huang Zhilong, Lu Zhanpeng, Tian Jingchang, Wang Guangjian, Gao Zhenli

机构信息

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Department of Urology, Jining No. 1 People's Hospital, Jining, Shandong 528000, P.R. China.

出版信息

Mol Med Rep. 2015 Nov;12(5):6997-7004. doi: 10.3892/mmr.2015.4260. Epub 2015 Aug 28.

DOI:10.3892/mmr.2015.4260
PMID:26323945
Abstract

MicroRNAs (miRNAs) are non-coding RNAs that function as regulators of tumor suppressors and oncogenes. A G>C polymorphism (rs2910164) in the miR‑146a precursor sequence leads to a functional change associated with a risk for various types of malignancy. The role of this single nucleotide polymorphism in the pathogenesis of renal cell carcinoma (RCC) has not yet been examined. The present study evaluated the association between rs2910164 genotypes and the risk and prognosis of RCC in a population comprised of 421 RCC cases and 432 controls. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for rs2910164 genotypes according to case status. Cox proportional hazards regression modeling was used to estimate hazards ratios and 95% CIs according to the genotypes among the RCC patients. It was found that the rs2910164 GG and GC genotypes were associated with an increased risk of RCC only in senior subjects (>57‑years old; adjusted OR=1.59, 95% CI=1.04‑2.43). Furthermore, the GC and GG genotypes were associated with a poorer survival rate among patients with RCC compared with the CC genotype (P=0.002). In conclusion, the observed association between the GG and GC genotype and poorer survival rate of RCC was at least partially mediated by the decreased expression of miR-146a.

摘要

微小RNA(miRNA)是一类非编码RNA,可作为肿瘤抑制因子和癌基因的调节因子。miR-146a前体序列中的G>C多态性(rs2910164)导致功能改变,与多种恶性肿瘤风险相关。该单核苷酸多态性在肾细胞癌(RCC)发病机制中的作用尚未得到研究。本研究评估了rs2910164基因型与421例RCC病例和432例对照人群中RCC风险及预后之间的关联。根据病例状态,采用无条件逻辑回归估计rs2910164基因型的比值比(OR)和95%置信区间(CI)。在RCC患者中,采用Cox比例风险回归模型根据基因型估计风险比和95%CI。结果发现,rs2910164的GG和GC基因型仅在老年受试者(>57岁;校正OR=1.59,95%CI=1.04-2.43)中与RCC风险增加相关。此外,与CC基因型相比,RCC患者中GC和GG基因型与较差的生存率相关(P=0.002)。总之,观察到的GG和GC基因型与RCC较差生存率之间的关联至少部分是由miR-146a表达降低介导的。

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