微小RNA中的五个常见功能多态性（rs2910164、rs2292832、rs11614913、rs3746444、rs895819）与乳腺癌易感性：来自8361例癌症病例和8504例对照的证据。
Five common functional polymorphisms in microRNAs (rs2910164, rs2292832, rs11614913, rs3746444, rs895819) and the susceptibility to breast cancer: evidence from 8361 cancer cases and 8504 controls.
作者信息
Dai Zhi-Jun, Shao Yong-Ping, Wang Xi-Jing, Xu Dan, Kang Hua-Feng, Ren Hong-Tao, Min Wei-Li, Lin Shuai, Wang Meng, Song Zhang-Jun
机构信息
Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
出版信息
Curr Pharm Des. 2015;21(11):1455-63. doi: 10.2174/1381612821666141208143533.
OBJECTIVES
To evaluate the relationship between the five common polymorphisms in miRNAs (miR-146a rs2910164 G>C, miR-149 rs2292832 C>T, miR-196a2 rs11614913 C>T, miR-499 rs3746444 A>G and miR-27a rs895819 A>G), and breast cancer (BC) risk.
METHODS
Meta-analyses were performed on 15 published studies involving 8, 361 BC patients and 8, 504 cancer-free controls. There were 8 studies with 4, 314 cases and 4, 485 controls for rs2910164, 3 studies with 1, 439 cases and 1, 508 controls for rs2292832, 10 studies with 4, 618 cases and 5, 590 controls for rs11614913, 5 studies with 2, 924 cases and 3, 563 controls for rs3746444, and 5 studies with 2, 912 cases and 3, 697 controls for rs895819. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the BC risk.
RESULTS
Meta-analyses showed that rs2910164 (miR-146a) was associated with BC risk in Caucasian population (homozygote comparison: OR = 1.29, 95%CI = 1.02-1.63, P=0.03; dominant model: OR = 1.31, 95% CI = 1.05-1.65, P=0.02), whereas negative results were obtained for Asians in all genetic models. rs11614913 (miR-196a2) was associated with BC risk in the overall population based on the recessive model (OR = 0.89, 95% CI = 0.80-0.99, P=0.03). Association of rs3746444 (miR-499) with BC risk was detected under three genetic models (allele contrast genetic model: OR = 1.13, 95%CI = 1.03-1.23, P=0.007; homozygote comparison: OR = 1.36, 95 %CI = 1.10-1.69, P=0.005 and recessive model: OR = 1.38, 95% CI = 1.12-1.70, P=0.003). When stratified by ethnicity, the effects remained in Asians. rs895819 (miR-27a) was associated with BC risk in the overall population based on the allele contrast genetic model (OR = 0.91, 95%CI = 0.85-0.98, P=0.02); heterozygote comparison (OR = 0.89, 95 %CI = 0.80-0.99, P=0.03) and the dominant model (OR = 0.89, 95% CI = 0.80-0.98, P=0.02). However, there was no association between rs2292832 (miR-149) polymorphism and BC susceptibility.
CONCLUSION
Our meta-analysis results suggested that the rs2910164 and rs3746444 polymorphisms are associated with increased BC risk, while the rs11614913 and rs895819 polymorphisms correlate with reduced BC risk.
目的
评估微小RNA（miR-146a rs2910164 G>C、miR-149 rs2292832 C>T、miR-196a2 rs11614913 C>T、miR-499 rs3746444 A>G和miR-27a rs895819 A>G）中的五种常见多态性与乳腺癌（BC）风险之间的关系。
方法
对15项已发表的研究进行荟萃分析，这些研究涉及8361例BC患者和8504例无癌对照。对于rs2910164，有8项研究，共4314例病例和4485例对照；对于rs2292832，有3项研究，共1439例病例和1508例对照；对于rs11614913，有10项研究，共4618例病例和5590例对照；对于rs3746444，有5项研究，共2924例病例和3563例对照；对于rs895819，有5项研究，共2912例病例和3697例对照。采用汇总比值比（OR）和95%置信区间（CI）来评估BC风险。
结果
荟萃分析表明，rs2910164（miR-146a）在白种人群中与BC风险相关（纯合子比较：OR = 1.29，95%CI = 1.02 - 1.63，P = 0.03；显性模型：OR = 1.31，95%CI = 1.05 - 1.65，P = 0.02），而在所有遗传模型中亚洲人的结果均为阴性。基于隐性模型，rs11614913（miR-196a2）在总体人群中与BC风险相关（OR = 0.89，95%CI = 0.80 - 0.99，P = 0.03）。在三种遗传模型下检测到rs3746444（miR-499）与BC风险相关（等位基因对比遗传模型：OR = 1.13，95%CI = 1.03 - 1.23，P = 0.007；纯合子比较：OR = 1.36，95%CI = 1.10 - 1.69，P = 0.005；隐性模型：OR = 1.38，95%CI = 1.12 - 1.70，P = 0.003）。按种族分层时，亚洲人群中仍存在这种关联。基于等位基因对比遗传模型，rs895819（miR-27a）在总体人群中与BC风险相关（OR = 0.91，95%CI = 0.85 - 0.98，P = 0.02）；杂合子比较（OR = 0.89，95%CI = 0.80 - 0.99，P = 0.03）和显性模型（OR = 0.89，95%CI = 0.80 - 0.98，P = 0.02）。然而，rs2292832（miR-149）多态性与BC易感性之间无关联。
结论
我们的荟萃分析结果表明，rs2910164和rs3746444多态性与BC风险增加相关，而rs11614913和rs895819多态性与BC风险降低相关。
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