Yu Xin, Zhang Yuan, Liu Shuang, Mu Yu, Shang Fengjia, Zhang Nan
Department of Pediatric Oncology, The First Hospital of Jilin University.
Department of Nursing, Eastern Division, The First Hospital of Jilin University.
Medicine (Baltimore). 2020 Jul 2;99(27):e20713. doi: 10.1097/MD.0000000000020713.
The Wilms tumor-1 (WT1) protein is an important regulator of malignant hematopoiesis and has been implicated in the pathogenesis of acute myeloid leukemia (AML). Recently special attention has been paid to the relationship of the WT1 single nucleotide polymorphism (SNP) rs16754 with AML risk and outcome, but the conflicting results made it difficult to draw definitive conclusions. In the present study, we systematically reviewed the literature and performed a meta-analysis of existing evidence. We searched Embase, Pubmed, Web of Science, Medline, Cochrane Library, Wanfang, and China National Knowledge Infrastructure databases using predefined search methodology for relevant studies. We pooled odd ratio (OR) with 95% confidence intervals (95% CI) to evaluate the association between SNP rs16754 and AML risk. In addition, we analyzed hazard ratio (HR) with 95% CI for overall survive, relapse-free survival, and disease-free survival. Q-statistic was used to assess the homogeneity and Egger test was used to evaluate publication bias. Eleven studies met the inclusion criteria for analysis. The results of fixed-effect meta-analyses revealed no association between SNP rs16754 and AML risk (AA + GA vs GG: OR = 0.92, 95% CI: 0.71-1.19, P = .518; AA vs GA + GG: OR = 1.23, 95% CI: 0.86-1.76, P = .262; AA vs GG: OR = 1.05, 95% CI: 0.68-1.63, P = .820; AG vs AA: OR = 0.77, 95% CI: 0.53-1.13, P = .186; AG vs GG: OR = 0.89, 95% CI: 0.68-1.16, P = .376). In subgroup analysis by race, age, and disease type, we did not find any significant association. However, the presence of rs16754 GA/GG genotype was associated with improved overall survive (HR = 0.48, 95% CI: 0.26-0.91, P = .024) and relapse-free survival (HR = 0.82, 95% CI: 0.68-1.00, P = .048) compared with the rs16754 AA. In summary, the WT1 SNP rs16754 was not associated with AML risk, but it had a significant impact on clinical outcome in AML patients.
威尔姆斯瘤-1（WT1）蛋白是恶性造血的重要调节因子，与急性髓系白血病（AML）的发病机制有关。最近，WT1单核苷酸多态性（SNP）rs16754与AML风险及预后的关系受到了特别关注，但相互矛盾的结果使得难以得出明确结论。在本研究中，我们系统回顾了文献并对现有证据进行了荟萃分析。我们使用预定义的搜索方法在Embase、Pubmed、Web of Science、Medline、Cochrane图书馆、万方和中国知网数据库中搜索相关研究。我们汇总了比值比（OR）及95%置信区间（95%CI）以评估SNP rs16754与AML风险之间的关联。此外，我们分析了总生存、无复发生存和无病生存的风险比（HR）及95%CI。Q统计量用于评估同质性，Egger检验用于评估发表偏倚。11项研究符合纳入分析的标准。固定效应荟萃分析结果显示，SNP rs16754与AML风险之间无关联（AA + GA vs GG：OR = 0.92，95%CI：0.71 - 1.19，P = 0.518；AA vs GA + GG：OR = 1.23，95%CI：0.86 - 1.76，P = 0.262；AA vs GG：OR = 1.05，95%CI：0.68 - 1.63，P = 0.820；AG vs AA：OR = 0.77，95%CI：0.53 - 1.13，P = 0.186；AG vs GG：OR = 0.89，95%CI：0.68 - 1.16，P = 0.376）。在按种族、年龄和疾病类型进行的亚组分析中，我们未发现任何显著关联。然而，与rs16754 AA基因型相比，rs16754 GA/GG基因型的存在与总生存改善（HR = 0.48，95%CI：0.26 - 0.91，P = 0.024）和无复发生存改善（HR = 0.82，95%CI：0.68 - 1.00，P = 0.048）相关。总之，WT1 SNP rs16754与AML风险无关，但对AML患者的临床结局有显著影响。
