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

Ambatipudi S 1 , Cuenin C 1 , Hernandez-Vargas H 1 , Ghantous A 1 , Le Calvez-Kelm F 1 , Kaaks R 2 Show all authors , Barrdahl M 2 , Boeing H 3 , Aleksandrova K 3 , Trichopoulou A 4 , Lagiou P 4 , Naska A 4 , Palli D 5 , Krogh V 6 , Polidoro S 7 , Tumino R 8 , Panico S 9 , Bueno-de-Mesquita B 10 , Peeters PH 11 , Quirós JR 12 , Navarro C 13 , Ardanaz E 14 , Dorronsoro M 15 , Key T 16 , Vineis P 17 , Murphy N 17 , Riboli E 17 , Romieu I 1 , Herceg Z 1

Affiliations 

  • 1 International Agency for Research on Cancer (IARC), Lyon, France
  • 2 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 3 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
  • 4 Hellenic Health Foundation, Athens, Greece
  • 5 Molecular & Nutritional Epidemiology Unit, Cancer Research & Prevention Institute-ISPO, Florence, Italy
  • 6 Epidemiology & Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
  • 7 Human Genetic Foundation (HuGeF), Torino, Italy
  • 8 Cancer Registry & Histopathology Unit, 'Civic MP Arezzo' Hospital, ASP Ragusa, Italy
  • 9 Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
  • 10 Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health & the Environment (RIVM), Bilthoven, The Netherlands
  • 11 Department of Epidemiology, Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  • 12 Public Health Directorate, Asturias, Spain
  • 13 Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
  • 14 CIBER Epidemiología y Salud Pública (CIBERESP), Spain
  • 15 Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain
  • 16 Cancer Epidemiology Unit, University of Oxford, Oxford, UK
  • 17 School of Public Health, Imperial College London, London, UK
Epigenomics, 2016 May;8(5):599-618.
PMID: 26864933 DOI: 10.2217/epi-2016-0001

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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