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

Srikant Ambatipudi, Cyrille Cuenin, Hector Hernandez-Vargas, Akram Ghantous, Florence Le Calvez-Kelm, Rudolf Kaaks, Myrto Barrdahl, Heiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Pagona Lagiou, Androniki Naska, Domenico Palli, Vittorio Krogh, Silvia Polidoro, Rosario Tumino, Salvatore Panico, Bas Bueno-De-Mesquita, Petra HM Peeters, José Ramón QuirósCarmen Navarro, Eva Ardanaz, Miren Dorronsoro, Tim Key, Paolo Vineis, Neil Murphy, Elio Riboli, Isabelle Romieu, Zdenko Herceg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 languageEnglish
Pages (from-to)599-618
Number of pages20
JournalEpigenomics
Volume8
Issue number5
DOIs
Publication statusPublished - 1 May 2016

Keywords

  • DNA methylome
  • epigenetic signature
  • prospective cohort
  • tobacco smoking

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