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AIM: Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure. MATERIALS & METHODS: Here, we examined the potential of DNA methylation changes in 910 prediagnostic peripheral blood samples as a marker of exposure to tobacco smoke in a large multinational cohort. RESULTS: We identified 748 CpG sites that were differentially methylated between smokers and nonsmokers, among which we identified novel regionally clustered CpGs associated with active smoking. Importantly, we found a marked reversibility of methylation changes after smoking cessation, although specific genes remained differentially methylated up to 22 years after cessation. CONCLUSION: Our study has comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation.

Original publication




Journal article



Publication Date





599 - 618


DNA methylome, epigenetic signature, prospective cohort, tobacco smoking, Adult, Aged, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Humans, Male, Middle Aged, Prospective Studies, Sequence Analysis, DNA, Smoking Cessation, Tobacco Smoking