Yu Jia-Yun, Hu Fan, Du Wei, Ma Xue-Lei, Yuan Kun
Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defect and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China.
J Chin Med Assoc. 2017 Apr;80(4):191-203. doi: 10.1016/j.jcma.2016.09.009. Epub 2017 Feb 8.
Recently, several studies have investigated the association between polymorphisms in miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs229283, miR-34b/c rs4938723, and hepatocellular carcinoma (HCC), which showed inconclusive results.
A publication search was performed in PubMed, ExcerptaMedica Database, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure to collect relevant medical data published through February 2016. The aim of this study was to ascertain the association between HCC and micro-RNAs. A total of 21 studies were included in our study, which showed that miR-146a rs2910164 polymorphism has a significant association with HCC in the allele, recessive, and homozygous models overall [allele model: odds ratio (OR) = 0.927, 95% confidence interval (CI): 0.869-0.988, p = 0.02; recessive model: OR = 0.893, 95% CI: 0.814-0.981, p = 0.018; homozygous model: OR = 0.853, 95% CI: 0.744-0.978, p = 0.023] and in Asian populations (allele model: OR = 0.921, 95% CI: 0.863-0.983, p = 0.014; recessive model: OR = 0.893, 95% CI: 0.814-0.981, p = 0.019; homozygous model: OR = 0.851, 95% CI: 0.741-0.977, p = 0.022). For miR-196a2 rs11614913, significant statistical heterogeneity overall and in Asian populations was identified in the comparison of the allele, recessive, homozygous, and heterozygous models (overall: allele model: OR = 0.889, 95% CI: 0.842-0.94, p < 0.001; recessive model: OR = 0.837, 95% CI: 0.723-0.970, p = 0.018; homozygous model: OR = 0.722, 95%CI: 0.575-0.906, p = 0.005; heterozygous model: OR = 0.532, 95% CI: 0.37-0.765, p = 0.001), and also has a decreased risk of HCC in Caucasians in all genetic models except for the heterozygous model (allele model: OR = 0.658, 95% CI: 0.49-0.885, p = 0.006; dominant model: OR = 0.641, 95% CI: 0.418-0.981, p = 0.041; recessive model: OR = 0.489, 95% CI: 0.278-0.862, p = 0.013; homozygous model: OR = 0.414, 95% CI: 0.222-0.772, p = 0.005). Only the recessive models produced a significant association between miR-499 rs3746444 polymorphism and HCC risk (recessive model: OR = 1.283, 95% CI: 1.008-1.632, p = 0.043).
The analysis for miR-146a rs2910164 polymorphisms by racial decent found the same association between miR-146a rs2910164 polymorphism and susceptibility to HCC in Asians, but no significance risk association was observed in Caucasians. The meta-analysis results showed that miR-196a2 rs11614913 was associated with a decreased risk of HCC in Caucasians in all genetic models except for the heterozygous model. In the Asian population, miR-499 rs3746444 polymorphism was associated with a decreased risk of HCC in recessive models. This meta-analysis showed that no significant statistical heterogeneity was identified in miR-149 rs2292832 and miR-34b/c rs4938723.
Our findings supported the proposition that the polymorphisms of miR-146a rs2910164, miR-196a2 rs11614913, and miR-196a2 rs11614913 may contribute to the susceptibility of HCC.
最近,多项研究探讨了miR-146a rs2910164、miR-196a2 rs11614913、miR-499 rs3746444、miR-149 rs229283、miR-34b/c rs4938723基因多态性与肝细胞癌(HCC)之间的关联,但结果尚无定论。
在PubMed、医学文摘数据库、中国生物医学文献数据库和中国知网进行文献检索,收集截至2016年2月发表的相关医学数据。本研究旨在确定HCC与微小RNA之间的关联。共纳入21项研究,结果显示,总体而言,miR-146a rs2910164基因多态性在等位基因、隐性和纯合子模型中与HCC存在显著关联[等位基因模型:比值比(OR)=0.927,95%置信区间(CI):0.869 - 0.988,p = 0.02;隐性模型:OR = 0.893,95% CI:0.814 - 0.981,p = 0.018;纯合子模型:OR = 0.853,95% CI:0.744 - 0.978,p = 0.023],在亚洲人群中也存在显著关联(等位基因模型:OR = 0.921,95% CI:0.863 - 0.983,p = 0.014;隐性模型:OR = 0.893,95% CI:0.814 - 0.981,p = 0.019;纯合子模型:OR = 0.851,95% CI:0.741 - 0.977,p = 0.022)。对于miR-196a2 rs11614913,在等位基因、隐性、纯合子和杂合子模型的比较中,总体及亚洲人群均存在显著的统计学异质性(总体:等位基因模型:OR = 0.889,95% CI:0.842 - 0.94,p < 0.001;隐性模型:OR = 0.837,95% CI:0.723 - 0.970,p = 0.018;纯合子模型:OR = 0.722,95% CI:0.575 - 0.906,p = 0.005;杂合子模型:OR = 0.532,95% CI:0.37 - 0.765,p = 0.001),并且在除杂合子模型外的所有遗传模型中,高加索人群患HCC的风险均降低(等位基因模型:OR = 0.658,95% CI:0.49 - 0.885,p = 0.006;显性模型:OR = 0.641,95% CI:0.418 - 0.981,p = 0.041;隐性模型:OR = 0.489,95% CI:0.278 - 0.862,p = 0.013;纯合子模型:OR = 0.414,95% CI:0.222 - 0.772,p = 0.005)。仅隐性模型显示miR-499 rs3746444基因多态性与HCC风险存在显著关联(隐性模型:OR = 1.283,95% CI:1.008 - 1.632,p = 0.043)。
按种族对miR-146a rs2910164基因多态性进行分析发现,miR-146a rs2910164基因多态性与亚洲人患HCC的易感性之间存在相同关联,但在高加索人群中未观察到显著的风险关联。荟萃分析结果显示,在除杂合子模型外的所有遗传模型中,miR-196a2 rs11614913与高加索人群患HCC风险降低相关。在亚洲人群中,miR-499 rs3746444基因多态性在隐性模型中与患HCC风险降低相关。该荟萃分析表明,miR-149 rs2292832和miR-34b/c rs4938723未发现显著的统计学异质性。
我们的研究结果支持以下观点,即miR-146a rs2910164、miR-196a2 rs11614913和miR-499 rs3746444基因多态性可能与HCC易感性有关。