Fang Fang, Andersen Allan M, Philibert Robert, Hancock Dana B
GenOmics, Bioinformatics, and Translational Research Center, RTI International, 3040 East Cornwallis Road, P.O. Box 12194, Research Triangle Park, NC 27709, USA.
Department of Psychiatry, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Addict Neurosci. 2023 Jun;6. doi: 10.1016/j.addicn.2023.100079. Epub 2023 Mar 1.
Cigarette smoking has been associated with epigenetic alterations that may be reversible upon cessation. As the most-studied epigenetic modification, DNA methylation is strongly associated with smoking exposure, providing a potential mechanism that links smoking to adverse health outcomes. Here, we reviewed the reversibility of DNA methylation in accessible peripheral tissues, mainly blood, in relation to cigarette smoking cessation and the utility of DNA methylation as a biomarker signature to differentiate current, former, and never smokers and to quantify time since cessation. We summarized thousands of differentially methylated Cytosine-Guanine (CpG) dinucleotides and regions associated with smoking cessation from candidate gene and epigenome-wide association studies, as well as the prediction accuracy of the multi-CpG predictors for smoking status. Overall, there is robust evidence for DNA methylation signature of cigarette smoking cessation. However, there are still gaps to fill, including (1) cell-type heterogeneity in measuring blood DNA methylation; (2) underrepresentation of non-European ancestry populations; (3) limited longitudinal data to quantitatively measure DNA methylation after smoking cessation over time; and (4) limited data to study the impact of smoking cessation on other epigenetic features, noncoding RNAs, and histone modifications. Epigenetic machinery provides promising biomarkers that can improve success in smoking cessation in the clinical setting. To achieve this goal, larger and more-diverse samples with longitudinal measures of a broader spectrum of epigenetic marks will be essential to developing a robust DNA methylation biomarker assay, followed by meeting validation requirements for the assay before being implemented as a clinically useful tool.
吸烟与表观遗传改变有关，戒烟后这些改变可能是可逆的。作为研究最多的表观遗传修饰，DNA甲基化与吸烟暴露密切相关，为吸烟与不良健康后果之间提供了一种潜在机制。在此，我们综述了可及外周组织（主要是血液）中DNA甲基化与戒烟相关的可逆性，以及DNA甲基化作为生物标志物特征用于区分当前吸烟者、既往吸烟者和从不吸烟者以及量化戒烟时间的效用。我们总结了来自候选基因和全表观基因组关联研究的数千个与戒烟相关的差异甲基化胞嘧啶-鸟嘌呤（CpG）二核苷酸和区域，以及多CpG预测因子对吸烟状态的预测准确性。总体而言，有充分证据支持戒烟的DNA甲基化特征。然而，仍有一些空白需要填补，包括：（1）测量血液DNA甲基化时的细胞类型异质性；（2）非欧洲血统人群代表性不足；（3）纵向数据有限，无法定量测量戒烟后随时间变化的DNA甲基化；（4）研究戒烟对其他表观遗传特征、非编码RNA和组蛋白修饰影响的数据有限。表观遗传机制提供了有前景的生物标志物，可提高临床戒烟成功率。为实现这一目标，拥有更广泛表观遗传标记纵向测量的更大、更多样化样本对于开发强大的DNA甲基化生物标志物检测至关重要，随后在作为临床有用工具实施之前满足该检测的验证要求。
