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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 investigate the relationship between DNA methylation in peripheral blood and cancer risk by Meta-analysis. Methods The systematic literature search was carried out in four English databases (PubMed, ISI WOK databases, Science Online, OVID) and three Chinese databases (CNKI, Wanfang and VIP) respectively. The keywords retrieved from English databases For DNA methylation, blood or leukocyte and cancer, tumor, carcinoma, neoplasm or malignancy, not limited to language, Chinese database search keywords for DNA methylation, peripheral blood or white blood cells and tumors or cancer. Literature quality assessment application Newcastle-Ottawa Scale (NOS). The overall odds ratio (OR) and 95% confidence interval (95% CI) were estimated using the fixed effects model (heterogeneity test I2 <25%) or random effects model (heterogeneity test I2≥25%). Results A total of 22 peripheral blood DNA methylation and 20 DNA methylation in peripheral blood were included in the analysis. Genomic DNA was hypomethylated in peripheral blood (OR = 1.34, 95% CI: 1.12-1.60, I2 = 89.1%, P = 0.001) and DNA hypermethylation (OR = 1.37, 95% CI: 1.24-1.52, I2 = 93.2%, P <0.001) at specific sites of peripheral blood increased the overall tumor risk. The subtype of tumor showed that the low methylation level of whole genome DNA in peripheral blood increased bladder cancer (OR = 1.96, 95% CI: 1.44-2.48, I2 = 85.1%, P = 0.001) (OR = 1.38, 95% CI: 1.08-1.68, I2 = 37.7%, P = 0.170), and hepatocellular carcinoma (OR = 1.38, 95% CI: 1.36-2.35, I2 = , 95% CI: 1.03-1.73, I2 = 77.3%, P = 0.012). Conclusion There is a correlation between DNA methylation and tumorigenesis in peripheral blood, which may be an important biomarker for epidemiological screening.