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Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts

Author

Listed:
  • Francesca Fasanelli

    (Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation
    Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin, Center for Cancer Prevention)

  • Laura Baglietto

    (Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health
    Paris-South University
    Cancer Epidemiology Centre, Cancer Council of Victoria
    School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne)

  • Erica Ponzi

    (Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation)

  • Florence Guida

    (MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place)

  • Gianluca Campanella

    (MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place)

  • Mattias Johansson

    (International Agency for Research on Cancer
    Umeå University)

  • Kjell Grankvist

    (Umeå University)

  • Mikael Johansson

    (Umeå University)

  • Manuela Bianca Assumma

    (Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation)

  • Alessio Naccarati

    (Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation)

  • Marc Chadeau-Hyam

    (MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place)

  • Ugo Ala

    (Università di Torino)

  • Christian Faltus

    (DKFZ—German Cancer Research Center)

  • Rudolf Kaaks

    (DKFZ—German Cancer Research Center
    Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL))

  • Angela Risch

    (DKFZ—German Cancer Research Center
    Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL)
    University of Salzburg)

  • Bianca De Stavola

    (London School of Hygiene and Tropical Medicine)

  • Allison Hodge

    (Cancer Epidemiology Centre, Cancer Council of Victoria)

  • Graham G. Giles

    (Cancer Epidemiology Centre, Cancer Council of Victoria
    School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne)

  • Melissa C. Southey

    (Genetic Epidemiology Laboratory, University of Melbourne)

  • Caroline L. Relton

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol)

  • Philip C. Haycock

    (MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol)

  • Eiliv Lund

    (Department of Community Medicine UiT–The Arctic University of Norway)

  • Silvia Polidoro

    (Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation)

  • Torkjel M. Sandanger

    (Department of Community Medicine UiT–The Arctic University of Norway)

  • Gianluca Severi

    (Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation
    Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health
    Paris-South University
    Cancer Epidemiology Centre, Cancer Council of Victoria)

  • Paolo Vineis

    (Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation
    MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place)

Abstract

DNA hypomethylation in certain genes is associated with tobacco exposure but it is unknown whether these methylation changes translate into increased lung cancer risk. In an epigenome-wide study of DNA from pre-diagnostic blood samples from 132 case–control pairs in the NOWAC cohort, we observe that the most significant associations with lung cancer risk are for cg05575921 in AHRR (OR for 1 s.d.=0.37, 95% CI: 0.31–0.54, P-value=3.3 × 10−11) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31–0.56, P-value=3.9 × 10−10), previously shown to be strongly hypomethylated in smokers. These associations remain significant after adjustment for smoking and are confirmed in additional 664 case–control pairs tightly matched for smoking from the MCCS, NSHDS and EPIC HD cohorts. The replication and mediation analyses suggest that residual confounding is unlikely to explain the observed associations and that hypomethylation of these CpG sites may mediate the effect of tobacco on lung cancer risk.

Suggested Citation

  • Francesca Fasanelli & Laura Baglietto & Erica Ponzi & Florence Guida & Gianluca Campanella & Mattias Johansson & Kjell Grankvist & Mikael Johansson & Manuela Bianca Assumma & Alessio Naccarati & Marc , 2015. "Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts," Nature Communications, Nature, vol. 6(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10192
    DOI: 10.1038/ncomms10192
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    Cited by:

    1. Thomas Battram & Tom R. Gaunt & Caroline L. Relton & Nicholas J. Timpson & Gibran Hemani, 2022. "A comparison of the genes and genesets identified by GWAS and EWAS of fifteen complex traits," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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