Wang Tian-Yi, Huang Yin-Peng, Ma Ping
Institute of Tumors, The First Affiliated Hospital, China Medical University, Nanjing North Street No. 155, Shenyang, 110001, People's Republic of China.
Tumour Biol. 2014 Sep;35(9):9255-62. doi: 10.1007/s13277-014-2213-5. Epub 2014 Jun 17.
The aim of this study was to identify the correlations of a common polymorphism (rs6774494 A > G) in the EVI-1 gene targeted by micro-RNA (miRNA)-206/133b with the pathogenesis of breast cancer (BC). A total of 196 unrelated ethnic Han Chinese women diagnosed with primary BC were consecutively recruited and 200 healthy controls were randomly selected from the same population-based cohort. Direct PCR sequencing assay was used to detection of rs6774494 A > G polymorphism in the EVI-1 gene. Real-time quantitative PCR (RT-PCR) analysis was performed to verify the alterations of the EVI1 messenger RNA (mRNA) levels. Kaplan-Meier analysis was used to investigate and to estimate the survival outcomes for each endpoint. All statistical analyses were performed with SPSS software (version 18.0, SPSS, Chicago, IL). Our results demonstrated that the carriers of EVI-1 AG genotype were more likely to develop BC when compared with the EVI-1 GG genotype (P = 0.034, OR = 1.26, 95% CI = 1.02 ∼ 1.57). In addition, it was found that patients with the G (AG + GG) allele of EVI-1 genetic variants were associated with higher risk of BC compared with the EVI-1 AA genotype (OR = 1.26, 95% CI = 1.02 ∼ 1.54, P = 0.028). The results of a subgroup analysis stratified by menopause revealed that in female post-menopause subgroup patients with the EVI-1 G allele were correlated with a higher risk of BC than those with the EVI-1 AA genotype (OR = 1.31, 95% CI = 1.00 ∼ 1.72, P = 0.054). Kaplan-Meier analyses suggested that carriers of the G allele (AG + GG) were associated with poorer overall survival (OS) and progression-free survival (PFS) compared with those with AA genotype (OS P = 0.042; PFS P = 0.036, respectively). The correlation analysis showed that EVI-1 mRNA levels were negatively associated with miRNA-206/133b levels in the carriers of the G allele (AG + GG) (r = -1.274, P < 0.05). Our findings provide evidence that the EVI-1 rs6774494 G > A polymorphism targeted by miRNA-206/133b may contribute to the pathogenesis of BC.
本研究旨在确定微小RNA（miRNA）-206/133b靶向的EVI-1基因中常见多态性（rs6774494 A>G）与乳腺癌（BC）发病机制之间的相关性。连续招募了196名被诊断为原发性BC的无血缘关系的汉族女性，并从同一基于人群的队列中随机选择了200名健康对照。采用直接PCR测序法检测EVI-1基因中rs6774494 A>G多态性。进行实时定量PCR（RT-PCR）分析以验证EVI1信使核糖核酸（mRNA）水平的变化。采用Kaplan-Meier分析来研究和估计每个终点的生存结果。所有统计分析均使用SPSS软件（版本18.0，SPSS，伊利诺伊州芝加哥）进行。我们的结果表明，与EVI-1 GG基因型相比，EVI-1 AG基因型携带者患BC的可能性更高（P = 0.034，OR = 1.26，95%CI = 1.02 ∼ 1.57）。此外，发现EVI-1基因变异的G（AG + GG）等位基因患者与EVI-1 AA基因型相比，患BC的风险更高（OR = 1.26，95%CI = 1.02 ∼ 1.54，P = 0.028）。按绝经分层的亚组分析结果显示，在绝经后女性亚组中，携带EVI-1 G等位基因的患者患BC的风险高于携带EVI-1 AA基因型的患者（OR = 1.31，95%CI = 1.00 ∼ 1.72，P = 0.054）。Kaplan-Meier分析表明，与AA基因型携带者相比，G等位基因（AG + GG）携带者的总生存期（OS）和无进展生存期（PFS）较差（OS P = 0.042；PFS P = 0.036）。相关性分析表明，在G等位基因（AG + GG）携带者中，EVI-1 mRNA水平与miRNA-206/133b水平呈负相关（r = -1.274，P<0.05）。我们的研究结果提供了证据，表明miRNA-206/133b靶向的EVI-1 rs6774494 G>A多态性可能与BC的发病机制有关。
