外周血白细胞DNA甲基化与肿瘤发病相关性Meta分析

Meta analysis of the association between peripheral blood leukocyte DNA methylation level and cancer risk

目的通过Meta分析探讨外周血DNA甲基化与癌症风险相关性。方法分别在4个英文数据库（PubMed,ISI WOK databases,Science Online,OVID）和3个中文数据库（CNKI,万方和VIP）中系统检索文献,检索日期截至2013-08,英文数据库检索的主题词为DNA methylation,blood or leukocyte和cancer,tumor,carcinoma,neoplasm or malignancy,不限制语言,中文数据库检索的主题词为DNA甲基化,外周血或白细胞和肿瘤或癌。文献质量评估应用Newcastle-Ottawa Scale（NOS）。应用固定效应模型（异质性检验I2〈25%）或随机效应模型（异质性检验I2≥25%）估计总体比值比（OR）和95%可信区间（95%CI）。结果共有22项外周血全基因组DNA甲基化和20项外周血特定基因DNA甲基化研究纳入分析,外周血全基因组DNA低甲基化（OR=1.34,95%CI：1.12-1.60,I2=89.1%,P=0.001）和外周血特定位点DNA过甲基化（OR=1.37,95%CI：1.24-1.52,I2=93.2%,P〈0.001）增加肿瘤总体发病风险。肿瘤类型亚族分析发现,外周血全基因组DNA低甲基化水平增加膀胱癌（OR=1.96,95%CI：1.44-2.48,I2=85.1%,P=0.001）、结直肠癌（OR=1.85,95%CI：1.36-2.35,I2=61.1%,P=0.012）、胃癌（OR=1.38,95%CI：1.08-1.68,I2=37.7%,P=0.170）和肝细胞肝癌（OR=1.38,95%CI：1.03-1.73,I2=77.3%,P=0.012）的发病风险。结论外周血DNA甲基化水平与肿瘤发生存在相关性,可能成为流行病学人群筛查的重要生物指标。

OBJECTIVE To clarify the association between DNA methylation in peripheral blood leukocyte and cancer risk by a meta-analysis. METHODS We conducted a systematic search of the studies using 4 English databases （PubMed, ISI WOK databases, Science Online, OVID） and 3 Chinese databases （CNKI, WanFang, and VIP） before August 2013. The following key words was used： 1） DNA methylation; 2） blood or leukocyte; and 3） cancer, tumor, carcinoma, neoplasm or malignancy. A quality score was evaluated using NOS （Newcastle-Ottawa Scale）. Pooled odds ratio （OR） with 95 % confidence interval （CI） was calculated using fixed-effect model （I^2〈25 %） or DerSimonian and Laird random-effects model （I^2≥25%）. RESULTS A total of 22 studies of global hypomethylation and 20 studies.of loci-specific DNA methylation were included in the analysis. The global hypomethylation （OR= 1. 34, 95% CI： 1. 12- 1.60,I^2=89. 1%,P=0. 001） and the specific-loci DNA methylation （OR= 1.37,95%CI： 1.24-1. 52,I^2 =93.2%,P〈 0. 001） were significantly associated with increased cancer risk. The peripheral blood leukocyte global hypomethylation was significantly associated with increased risk of bladder cancer （OR： 1. 96, 95% CI： 1. 44- 2. 48, 12 = 85. 1%,P=0. 001）,colorectal cancer （OR：I. 85 95%CI：1.36-2.35,I^2 =61. 1%,P=0. 012）, gastric cancer（OR：1. 38,95%CI 1.08-1.68,I^2 = 37. 7%,P=0. 170） and hepatocellular carcinoma （OR： 1. 38,95%CI： 1.03- 1. 73,I^2 = 77. 3%,P= 0. 012）. CONCLUSION DNA in peripheral blood leukocyte is associated with cancer risk and may serve as a potential bi omarker of cancer risk.