Chen Chen, Yang Shenglan, Chaugai Sandip, Wang Yan, Wang Dao Wen
Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People's Republic of China.
Department of Internal Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
BMC Med Genet. 2014 Nov 30;15:126. doi: 10.1186/s12881-014-0126-1.
MicroRNAs (miRNAs) are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target mRNAs, and are involved in diverse biological and pathological processes. Single nucleotide polymorphisms (SNPs) which are located in the miRNA-coding genes may participate in the process of development and diseases by altering the expression of mature miRNA. Recent studies investigating the association between hsa-mir-499 polymorphism (rs3746444) and cancer risk have yielded conflicting results.
In this meta-analysis, we conducted a search of case-control studies on the associations of SNP rs3746444 with susceptibility to cancer in electronic databases. A total of 31 studies involving 12799 cases and 14507 controls were retrieved and the strength of the association was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Hardy-Weinberg equilibrium (HWE) was assessed by the goodness-of-fit chi-square test in controls. Subgroup analyses were done by racial descent and cancer type. Publication bias of literatures was evaluated by visual inspection of funnel plots and the linear regression asymmetry test by Egger et al. Sensitivity analysis was conducted by excluding one study at a time to examine the influence of individual data set on the pooled ORs.
Overall, significant association between rs3746444 polymorphism and susceptibility to cancer was identified in TC versus TT and TC/CC versus TT (dominant) models. In the stratified analyses, increased risks were found in Asians, but not in Caucasians in all comparison models tested. Moreover, significant association with an increased risk was found in Chinese population. Also, much higher significant association with increased cancer risks were found in Iranian population. In different cancer types, a decreased risk was found in esophageal cancer.
Our meta-analysis suggested that hsa-mir-499 rs3746444 T > C polymorphism is associated with the risk of cancer in Asians, mainly in Iranian and Chinese population. However, rs3746444 T > C polymorphism is negatively associated with the risk of esophageal cancer.
微小RNA（miRNA）是一类内源性、小分子非编码RNA，通过抑制翻译或降解靶mRNA在转录后水平负向调控基因表达，并参与多种生物学和病理过程。位于miRNA编码基因中的单核苷酸多态性（SNP）可能通过改变成熟miRNA的表达参与发育和疾病过程。最近关于hsa - mir - 499多态性（rs3746444）与癌症风险关联的研究结果相互矛盾。
在这项荟萃分析中，我们在电子数据库中检索了关于SNP rs3746444与癌症易感性关联的病例对照研究。共检索到31项研究，涉及12799例病例和14507例对照，并通过合并比值比（OR）和95%置信区间（CI）估计关联强度。通过对照中的拟合优度卡方检验评估哈迪 - 温伯格平衡（HWE）。按种族和癌症类型进行亚组分析。通过漏斗图的视觉检查和Egger等人的线性回归不对称检验评估文献的发表偏倚。通过一次排除一项研究进行敏感性分析，以检查单个数据集对合并OR的影响。
总体而言，在TC与TT以及TC/CC与TT（显性）模型中，鉴定出rs3746444多态性与癌症易感性之间存在显著关联。在分层分析中，在所有测试的比较模型中，亚洲人患癌风险增加，但高加索人未增加。此外，在中国人群中发现与患癌风险增加存在显著关联。而且，在伊朗人群中发现与患癌风险增加的显著关联程度更高。在不同癌症类型中，食管癌的风险降低。
我们的荟萃分析表明，hsa - mir - 499 rs3746444 T > C多态性与亚洲人，主要是伊朗和中国人群的癌症风险相关。然而，rs3746444 T > C多态性与食管癌风险呈负相关。
