He Hairong, Zhai Xiaoyu, Liu Xiaomin, Zheng Jie, Zhai Yajing, Gao Fan, Chen Yonghua, Lu Jun
Clinical Research Center.
Clinical Research Center; College of Pharmacy, Xi'an Medical University.
Onco Targets Ther. 2017 Mar 23;10:1793-1801. doi: 10.2147/OTT.S132503. eCollection 2017.
The NAD(P)H:quinone oxidoreductase (NQO1) C609T and C465T polymorphisms have been widely thought to be associated with the risk of acute leukemia (AL) in recent years, but the correlations are still unclear. A meta-analysis is generally acknowledged as one of the best methods for secondary research, and so it was applied in this study with the aim of elucidating how the NQO1 C609T and C465T polymorphisms are related to the risk of AL.
Relevant studies were searched in the PubMed, EMBASE, CNKI, and Wanfang databases, and the obtained data were analyzed using Stata (version 12.1). The allele-contrast model was applied, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationship strengths. Meta-regression was used to identify sources of heterogeneity, and subgroup analyses were conducted. Publication bias was analyzed using funnel plots, with the trim-and-fill method used to analyze the effect of publication bias on pooled results. In addition, sensitivity analysis, the fail-safe number method, and cumulative analysis by publication year were performed to measure the stability of the obtained results.
This meta-analysis included 28 relevant studies involving 5,953 patients and 8,667 controls. Overall, the C609T polymorphism was associated with the risk of acute lymphoblastic leukemia (ALL; OR =1.18, 95% CI =1.00-1.39, =0.05). Meanwhile, race was found to be a potential source of heterogeneity for the relationship between the C609T polymorphism and acute myeloid leukemia (AML) risk, and the subgroup analysis identified the C609T polymorphism as a risk factor for AML in Asians (OR =1.34, 95% CI =1.03-1.74, =0.03). The number of studies about C465T polymorphism was too small to pool the data.
There are increased risks of ALL in all subjects and of AML in Asians for carriers of the NQO1 C609T polymorphism. Further studies are needed to verify the associations of the C465T polymorphism with the risk of AL.
近年来,人们普遍认为烟酰胺腺嘌呤二核苷酸磷酸(NAD(P)H):醌氧化还原酶1(NQO1)基因C609T和C465T多态性与急性白血病(AL)风险相关,但两者之间的相关性仍不明确。荟萃分析通常被认为是二次研究的最佳方法之一,因此本研究采用该方法,旨在阐明NQO1基因C609T和C465T多态性与AL风险之间的关系。
在PubMed、EMBASE、中国知网(CNKI)和万方数据库中检索相关研究,并使用Stata(12.1版)对获得的数据进行分析。采用等位基因对比模型,使用比值比(OR)及95%置信区间(CI)评估关联强度。采用Meta回归分析异质性来源,并进行亚组分析。使用漏斗图分析发表偏倚,并采用剪补法分析发表偏倚对合并结果的影响。此外,进行敏感性分析、失效安全数法分析及按发表年份进行累积分析,以衡量所得结果的稳定性。
本荟萃分析纳入了28项相关研究,涉及5953例患者和8667例对照。总体而言,C609T多态性与急性淋巴细胞白血病(ALL)风险相关(OR = 1.18,95%CI = 1.00 - 1.39,P = 0.05)。同时,种族被发现是C609T多态性与急性髓系白血病(AML)风险之间关系的潜在异质性来源,亚组分析确定C609T多态性是亚洲人患AML的危险因素(OR = 1.34,95%CI = 1.03 - 1.74,P = 0.03)。关于C465T多态性的研究数量过少,无法汇总数据。
对于NQO1基因C609T多态性携带者,所有受试者患ALL的风险增加,亚洲人患AML的风险增加。需要进一步研究来验证C465T多态性与AL风险之间的关联。