Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study

Epigenomics. 2016 May;8(5):599-618. doi: 10.2217/epi-2016-0001. Epub 2016 Feb 11.


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.

Keywords: DNA methylome; epigenetic signature; prospective cohort; tobacco smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Sequence Analysis, DNA
  • Smoking Cessation
  • Tobacco Smoking / genetics*