Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Bavaria, Germany.
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Bavaria, Germany.
BMC Genomics. 2017 Oct 18;18(1):805. doi: 10.1186/s12864-017-4198-0.
The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking.
Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive.
This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
通过横断面研究，越来越多的证据表明吸烟与 DNA 甲基化之间存在全基因组关联。然而，很少有大规模的研究通过对多个时间点的个体进行观察来探索这些关联。在这里，我们使用 Illumina 450K BeadChip 并在大约 7 年的时间内收集了两个时间点的数据，研究了与戒烟或继续吸烟相关的、随时间变化的甲基化变化，以及与持续吸烟相关的甲基化变化。
我们的研究结果表明，戒烟后，改变的甲基化最快在最初的二十年就开始逆转，逆转率与最初的甲基化差异有关。对于 52 个 CpG 位点，与从不吸烟者相比，以前吸烟者的基线到随访的甲基化变化明显不同（最低 p 值为 3.61 x 10，基因 AHRR，cg26703534）。这些位点的大部分区域先前都与与吸烟相关的疾病有关。尽管早期快速变化，但即使在戒烟四十年后，以前吸烟者的甲基化动态似乎比从不吸烟者更大。此外，我们的研究揭示了持续吸烟的异质性影响：一些位点的甲基化水平在吸烟者和非吸烟者之间进一步分化，而其他位点则重新接近。尽管吸烟习惯的强度似乎比持续时间更重要，但结果仍不确定。
这项研究增进了我们对吸烟与甲基化之间动态联系的理解，揭示了戒烟几十年后甲基化水平的持续波动，并表明继续吸烟可能会产生一系列影响。这些结果可以促进对吸烟引起的甲基化紊乱背后分子机制的深入了解，提高过去吸烟行为生物标志物开发的可能性，并增加对暴露于疾病的分子途径的理解。
