title: Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study.
abstract: Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our study has comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation.
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Srikant
authors: S
authors: Ambatipudi
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Cyrille
authors: C
authors: Cuenin
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Hector
authors: H
authors: Hernandez-Vargas
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Akram
authors: A
authors: Ghantous
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Florence
authors: F
authors: Le Calvez-Kelm
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Rudolf
authors: R
authors: Kaaks
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Myrto
authors: M
authors: Barrdahl
authors: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors: Heiner
authors: H
authors: Boeing
authors: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors: Krasimira
authors: K
authors: Aleksandrova
authors: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition & Health, Unit of Nutritional Epidemiology & Nutrition in Public Health, Department of Hygiene, Epidemiology & Medical Statistics, University of Athens Medical School, Athens, Greece.
authors: Antonia
authors: A
authors: Trichopoulou
authors: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition & Health, Unit of Nutritional Epidemiology & Nutrition in Public Health, Department of Hygiene, Epidemiology & Medical Statistics, University of Athens Medical School, Athens, Greece.
authors: Pagona
authors: P
authors: Lagiou
authors: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition & Health, Unit of Nutritional Epidemiology & Nutrition in Public Health, Department of Hygiene, Epidemiology & Medical Statistics, University of Athens Medical School, Athens, Greece.
authors: Androniki
authors: A
authors: Naska
authors: Molecular & Nutritional Epidemiology Unit, Cancer Research & Prevention Institute-ISPO, Florence, Italy.
authors: Domenico
authors: D
authors: Palli
authors: Epidemiology & Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors: Vittorio
authors: V
authors: Krogh
authors: Human Genetic Foundation (HuGeF), Torino, Italy.
authors: Silvia
authors: S
authors: Polidoro
authors: Cancer Registry & Histopathology Unit, 'Civic MP Arezzo' Hospital, ASP Ragusa, Italy.
authors: Rosario
authors: R
authors: Tumino
authors: Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
authors: Salvatore
authors: S
authors: Panico
authors: Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health & the Environment (RIVM), Bilthoven, The Netherlands.|Department of Gastroenterology & Hepatology, University Medical Centre, Utrecht, The Netherlands.|Department of Epidemiology & Biostatistics, The School of Public Health, Imperial College London, London, UK.|Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Bas
authors: B
authors: Bueno-de-Mesquita
authors: Department of Epidemiology, Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.|MRC-PHE Centre for Environment & Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK.
authors: Petra Hm
authors: PH
authors: Peeters
authors: Public Health Directorate, Asturias, Spain.
authors: José Ramón
authors: JR
authors: Quirós
authors: Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Department of Health & Social Sciences, Universidad de Murcia, Spain.
authors: Carmen
authors: C
authors: Navarro
authors: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Public Health Institute of Navarra, Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors: Eva
authors: E
authors: Ardanaz
authors: Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain.
authors: Miren
authors: M
authors: Dorronsoro
authors: Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
authors: Tim
authors: T
authors: Key
authors: School of Public Health, Imperial College London, London, UK.
authors: Paolo
authors: P
authors: Vineis
authors: School of Public Health, Imperial College London, London, UK.
authors: Neil
authors: N
authors: Murphy
authors: School of Public Health, Imperial College London, London, UK.
authors: Elio
authors: E
authors: Riboli
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Isabelle
authors: I
authors: Romieu
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: Zdenko
authors: Z
authors: Herceg
mesh_terms: D000328:Adult; D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D016540:Smoking Cessation; D000073869:Tobacco Smoking / Q000235:genetics*
keywords: DNA methylome; epigenetic signature; prospective cohort; tobacco smoking