微小RNA中的五个常见功能多态性与乳腺癌易感性：一项更新的荟萃分析

Five Common Functional Polymorphisms in microRNAs and Susceptibility to Breast Cancer: An Updated Meta-Analysis.

作者信息

Wu Jie, Wang Yusi, Shang Lihua, Qi Lichun, Song Mowei

机构信息

1 Laboratory of Medical Genetics, Harbin Medical University , Harbin, China .

2 Department of Medical Oncology, Third Affiliated Hospital of Harbin Medical University , Harbin, China .

出版信息

Genet Test Mol Biomarkers. 2018 Jun;22(6):350-358. doi: 10.1089/gtmb.2017.0270. Epub 2018 May 21.

DOI:10.1089/gtmb.2017.0270

PMID:29782194

Abstract

AIMS

microRNAs (miRNA) play a key role in the pathogenesis of breast cancer (BC) as regulators of tumor-associated genes, and understanding their polymorphisms is critical to the control of breast carcinogenesis. Thus, the present study explored the association between five common functional polymorphisms in miRNAs (i.e., miRNA-196a2C>T, rs11614913; miRNA-146aG>C, rs2910164; miRNA-423C>A, rs6505162; miRNA-608G>C, rs4919510; miRNA-27aC>T, rs895819) and the risk of BC.

MATERIALS AND METHODS

Meta-analyses were performed on 31 studies, including 14,677 BC patients and 16,143 cancer-free controls. Fourteen studies with 6147 cases and 5820 controls were analyzed for rs2910164, seventeen studies with 7021 cases and 8186 controls were analyzed for rs11614913, seven studies with 1891 (3390) cases and 2239 (5485) controls were analyzed for rs6505162 and rs4919510, respectively, and nine studies with 4499 cases and 5434 controls were analyzed for rs895819. Odds ratios (ORs) and 95% confidence intervals (CIs) were adopted to estimate BC risk. Subgroup analyses were performed for ethnicity. Because there was one study with mixed ethnicities, 16 studies were used in the analysis of Caucasian groups, and 16 studies were used for the Asian group.

RESULT

Meta-analysis showed that rs895819 correlated with reduced BC risk in three genotypic models: allele (Caucasian: OR = 0.89, 95% CI = 0.82-0.97, p = 0.008; Total: OR = 0.93, 95% CI = 0.87-0.99, p = 0.03), recessive (Caucasian: OR = 0.85, 95% CI = 0.77-0.94, p = 0.002; Total: OR = 0.92, 95% CI = 0.85-0.99, p = 0.04), and dominant (Total: OR = 0.87, 95% CI = 0.77-0.99, p = 0.04). Of note, a significant publication bias for rs895819 was observed in the dominant model. Unexpectedly, the other four polymorphisms were not associated with BC risk in any of the models.

CONCLUSIONS

The present study indicates that only the rs895819 polymorphism was associated with BC risk.

摘要

目的

微小RNA（miRNA）作为肿瘤相关基因的调节因子，在乳腺癌（BC）发病机制中起关键作用，了解其多态性对于控制乳腺癌发生至关重要。因此，本研究探讨了miRNA中的五个常见功能多态性（即miRNA - 196a2C>T，rs11614913；miRNA - 146aG>C，rs2910164；miRNA - 423C>A，rs6505162；miRNA - 608G>C，rs4919510；miRNA - 27aC>T，rs895819）与BC风险之间的关联。

材料与方法

对31项研究进行荟萃分析，包括14677例BC患者和16143例无癌对照。对14项研究（6147例病例和5820例对照）分析rs2910164，对17项研究（7021例病例和8186例对照）分析rs11614913，对7项研究（分别为1891例（3390例）病例和2239例（5485例）对照）分析rs6505162和rs4919510，对9项研究（4499例病例和5434例对照）分析rs895819。采用比值比（OR）和95%置信区间（CI）来估计BC风险。按种族进行亚组分析。由于有一项研究涉及混合种族，因此在白种人群组分析中使用了16项研究，在亚洲人群组分析中使用了16项研究。

结果

荟萃分析表明，在三种基因型模型中，rs895819与BC风险降低相关：等位基因（白种人：OR = 0.89，95% CI = 0.82 - 0.97，p = 0.008；总体：OR = 0.93，95% CI = 0.87 - 0.99，p = 0.03）、隐性（白种人：OR = 0.85，95% CI = 0.77 - 0.94，p = 0.002；总体：OR = 0.92，95% CI = 0.85 - 0.99，p = 0.04）和显性（总体：OR = 0.87，95% CI = 0.77 - 0.99，p = 0.04）。值得注意的是，在显性模型中观察到rs895819存在显著的发表偏倚。出乎意料的是，其他四个多态性在任何模型中均与BC风险无关。