Kim Mi Na, Kim Jung Oh, Lee Seung Min, Park Hana, Lee Ju Ho, Rim Kyu Sung, Hwang Seong Gyu, Kim Nam Keun
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
PLoS One. 2016 Sep 9;11(9):e0162279. doi: 10.1371/journal.pone.0162279. eCollection 2016.
Single-nucleotide polymorphisms (SNPs) in microRNA machinery genes might affect microRNA processing and subsequently impact tumorigenesis. The aim of this study was to investigate the associations between SNPs in microRNA machinery genes and hepatocellular carcinoma (HCC) in a Korean population. Genotyping of six SNPs in microRNA machinery genes was performed using blood samples from 147 patients with HCC and 209 healthy control subjects. None of the six SNPs in microRNA machinery genes were significantly associated with HCC development. However, among the models for six polymorphic loci-DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) and XPO5 (rs11077)-one allele combination (A-A-T-C-C-C) showed synergistic effects in terms of an increased risk of HCC development (odds ratio = 8.881, 95% confidence interval [CI] = 1.889-41.750; P = 0.002). Multivariate Cox proportional hazard regression analysis showed a significant survival benefit for the DICER rs3742330 GG compared with the AA type (hazard ratio [HR], 0.314; 95% CI, 0.135-0.730; P = 0.007) and for the RAN rs14035 CT compared with the CC genotype (HR, 0.587; 95% CI, 0.349-0.987; P = 0.044). Although we found no direct association between DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) or XPO5 (rs11077) polymorphisms and HCC risk, we demonstrated that DICER (rs3742330) and RAN (rs14035) were associated with the survival of HCC patients. Future studies with larger samples are needed to determine associations of SNPs in microRNA machinery genes with HCC risk and prognosis.
微小RNA机制基因中的单核苷酸多态性（SNP）可能影响微小RNA的加工，进而影响肿瘤发生。本研究旨在调查韩国人群中微小RNA机制基因中的SNP与肝细胞癌（HCC）之间的关联。使用147例HCC患者和209例健康对照者的血样对微小RNA机制基因中的6个SNP进行基因分型。微小RNA机制基因中的6个SNP均与HCC发生无显著关联。然而，在6个多态性位点的模型中——DICER（rs3742330和rs13078）、DROSHA（rs10719和rs6877842）、RAN（rs14035）和XPO5（rs11077）——一种等位基因组合（A - A - T - C - C - C）在HCC发生风险增加方面显示出协同效应（比值比 = 8.881，9５％置信区间[CI] = 1.889 - 41.750；P = 0.002）。多变量Cox比例风险回归分析显示，与AA型相比，DICER rs3742330 GG具有显著的生存获益（风险比[HR]，0.314；95％CI，0.135 - 0.730；P = 0.007），与CC基因型相比，RAN rs14035 CT具有显著的生存获益（HR，0.587；95％CI，0.349 - 0.987；P = 0.044）。虽然我们未发现DICER（rs3742330和rs13078）、DROSHA（rs10719和rs6877842）、RAN（rs14035）或XPO5（rs11077）多态性与HCC风险之间存在直接关联，但我们证明DICER（rs374233０）和RAN（rs14035）与HCC患者的生存相关。需要进行更大样本量的未来研究，以确定微小RNA机制基因中的SNP与HCC风险和预后的关联。
