Department of Radiation, Oncology Center, Qilu Hospital of Shandong University, Jinan, Peoples' Republic of China.
Mutagenesis. 2012 Nov;27(6):779-88. doi: 10.1093/mutage/ges052. Epub 2012 Sep 5.
MicroRNAs (miRNAs) are small non-coding RNA molecules, which act as post-transcriptional regulators of gene expression and have been implicated in initiation, progression and treatment outcome of diverse cancers. Single nucleotide polymorphisms (SNPs), as the most common type of genetic variation, also exist in miRNA genes and can lead to alteration in miRNA expression resulting in diverse functional consequences. Emerging studies have evaluated the association of miRNA SNPs with cancer risk, but the results remain inconclusive. To assess the relationship between miRNA SNPs and cancer risk, we performed a meta-analysis of 18 studies involving 20660 subjects for miR-146a rs2910164 polymorphism and 21 studies involving 26,018 subjects for miR-196a2 rs11614913 polymorphism. As for rs2910164, no significant association of cancer risk was found in the overall analysis. In subgroup analysis by cancer type, ethnicity, source of controls and sample size, significant association of cancer risk was mainly found in papillary thyroid carcinoma, primary liver cancer, cervical cancer, Caucasian population and small sample size studies. For rs11614913, significant results were found in all the tested genetic models and T allele or its carriers were associated with decreased cancer risk in overall analysis (T vs. C: OR = 0.888, 95% CI 0.84-0.938; TT+TC vs. CC: OR = 0.897, 95% CI 0.828-0.971). In stratified analysis by cancer type and ethnicity, significant association of cancer risk was observed in breast cancer, lung cancer, colorectal cancer and Asian population, but not in Caucasian population. During further stratified analysis by source of controls and sample size, results similar to those of overall analysis were found in all of the subgroups. Taken together, our results indicated that miR-196a2 rs11614913 T variant probably contribute to decreased susceptibility to cancer. However, limited evidence was found for association of miR-146a rs2910164 with cancer risk, and further well-designed studies with large sample size will be necessary to validate the effect of miR-146a rs2910164 on cancer susceptibility.
MicroRNAs (miRNAs) 是小的非编码 RNA 分子,作为基因表达的转录后调控因子,已被涉及到多种癌症的发生、发展和治疗结果。单核苷酸多态性(SNPs)作为最常见的遗传变异类型,也存在于 miRNA 基因中,可导致 miRNA 表达的改变,从而产生不同的功能后果。新兴研究评估了 miRNA SNPs 与癌症风险的相关性,但结果仍不确定。为了评估 miRNA SNPs 与癌症风险的关系,我们对涉及 20660 例个体的 miR-146a rs2910164 多态性的 18 项研究和涉及 26018 例个体的 miR-196a2 rs11614913 多态性的 21 项研究进行了荟萃分析。对于 rs2910164,在总体分析中未发现癌症风险的显著相关性。在按癌症类型、种族、对照来源和样本量进行的亚组分析中,主要在甲状腺乳头状癌、原发性肝癌、宫颈癌、白种人群和小样本量研究中发现癌症风险的显著相关性。对于 rs11614913,在所有测试的遗传模型中均发现了显著结果,且 T 等位基因或其携带者与总体分析中的癌症风险降低相关(T 与 C:OR=0.888,95%CI 0.84-0.938;TT+TC 与 CC:OR=0.897,95%CI 0.828-0.971)。在按癌症类型和种族进行的分层分析中,在乳腺癌、肺癌、结直肠癌和亚洲人群中观察到癌症风险的显著相关性,但在白种人群中未观察到。在进一步按对照来源和样本量进行的分层分析中,在所有亚组中均发现了与总体分析相似的结果。综上所述,我们的结果表明,miR-196a2 rs11614913 T 变异可能导致癌症易感性降低。然而,miR-146a rs2910164 与癌症风险的相关性证据有限,需要进一步设计更大样本量的研究来验证 miR-146a rs2910164 对癌症易感性的影响。