Background: Lung cancer (LC) is the leading cause of cancer deaths worldwide among both men and women, and represents a major public health challenge. DNA methylation (DNAm) has shown potential in identifying individuals at higher risk of LC, but the overall evidence has not been systematically evaluated. This review and meta-analysis aims to evaluate and summarize existing research on the association between blood DNAm levels and LC risk.Methods: Searches were conducted in PubMed, Web of Science, and Scopus for studies published until February 2024, following PRISMA and MOOSE guidelines. Eleven studies met the eligibility criteria.Results: Using a random effects model, our pooled analysis showed a significant association between increased DNAm levels and LC risk (OR 1.24, 95% CI 1.10–1.39; I2= 93.90%,p= 0.0001). Stratifying the results by study design showed a stronger association in two prospective cohort studies (OR 1.61; 95% CI 1.36–1.90; I2= 14.42%,p= 0.32), while case–control studies showed a weaker association (OR 1.05; 95% CI 0.99–1.11; I2= 70.57%,p= 0.0001). Sensitivity analyses indicated that omitting individual studies did not significantly alter the LC risk estimates.Conclusions: These findings suggest that higher blood DNAm levels are associated with an increased risk of LC, especially in long-term cohort studies. Further research is recommended to explore the potential of DNAm as a screening biomarker for LC and to clarify the role of other influencing factors.
背景：肺癌是全球男性和女性癌症死亡的首要原因，构成了一项重大的公共卫生挑战。DNA甲基化在识别肺癌高风险个体方面显示出潜力，但现有证据尚未得到系统评估。本综述与荟萃分析旨在评估和总结血液DNA甲基化水平与肺癌风险关联的现有研究。 方法：遵循PRISMA和MOOSE指南，在PubMed、Web of Science和Scopus数据库中检索截至2024年2月发表的研究。共11项研究符合纳入标准。 结果：采用随机效应模型进行合并分析，结果显示DNA甲基化水平升高与肺癌风险显著相关（OR 1.24，95% CI 1.10–1.39；I²= 93.90%，p= 0.0001）。按研究设计分层分析显示，两项前瞻性队列研究的关联性更强（OR 1.61；95% CI 1.36–1.90；I²= 14.42%，p= 0.32），而病例对照研究的关联性较弱（OR 1.05；95% CI 0.99–1.11；I²= 70.57%，p= 0.0001）。敏感性分析表明，剔除单项研究未显著改变肺癌风险估计值。 结论：这些发现提示，较高的血液DNA甲基化水平与肺癌风险增加相关，尤其是在长期队列研究中。建议进一步研究探索DNA甲基化作为肺癌筛查生物标志物的潜力，并明确其他影响因素的作用。
Methylation Biomarkers of Lung Cancer Risk: A Systematic Review and Meta-Analysis
肿瘤(癌症)患者之家