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miRNA 多态性与癌症风险的遗传关联研究和荟萃分析的综合综述。

Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

机构信息

Medical Genetics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, MD, USA.

出版信息

PLoS One. 2012;7(11):e50966. doi: 10.1371/journal.pone.0050966. Epub 2012 Nov 30.

DOI:10.1371/journal.pone.0050966
PMID:23226435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3511416/
Abstract

BACKGROUND

MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a two-sided meta-analytic approach.

METHODS

An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association.

RESULTS

Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC) while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096-1.481, P = 0.002). Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.

CONCLUSIONS

The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.

摘要

背景

微小 RNA(miRNA)是一种调节相应信使 RNA(mRNA)表达的小 RNA 分子。在多种人类恶性肿瘤的发生、发展和预后中,不同 miRNA 的表达水平变化已经被观察到。本研究旨在采用双侧荟萃分析方法,研究四个高度研究的 miRNA 多态性(mir-146a rs2910164、mir-196a2 rs11614913、mir-149 rs2292832 和 mir-499 rs3746444)与癌症风险之间的关联。

方法

对包含 27573 例癌症病例和 34791 例对照的 53 项独立病例对照研究进行了更新的荟萃分析。使用比值比(OR)和 95%置信区间(95%CI)来研究关联的强度。

结果

总体而言,合并分析显示 mir-196a2 rs11614913 与癌症风险降低相关(OR=0.846,P=0.004,TT 与 CC),而其他 miRNA SNPs 与总体癌症风险无关。还进行了基于癌症类型和种族的亚组分析,结果表明,在隐性模型下,miR-146a rs2910164 与高加索人群的总体癌症风险之间存在强烈关联(OR=1.274,95%CI=1.096-1.481,P=0.002)。按癌症类型分层分析也表明,mir-196a2 rs11614913 与肺癌和结直肠癌在等位基因和基因型水平上相关。

结论

本荟萃分析表明,mir-196a2 rs11614913 多态性与总体癌症风险(尤其是在亚洲人群中)具有重要作用。需要进一步进行大样本量的研究来评估和证实这种关联。

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