Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts
Identifieur interne : 002E65 ( Ncbi/Merge ); précédent : 002E64; suivant : 002E66Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts
Auteurs : Francesca Fasanelli [Italie] ; Laura Baglietto [France, Australie] ; Erica Ponzi [Italie] ; Florence Guida [Royaume-Uni] ; Gianluca Campanella [Royaume-Uni] ; Mattias Johansson [France, Suède] ; Kjell Grankvist [Suède] ; Mikael Johansson [Suède] ; Manuela Bianca Assumma [Italie] ; Alessio Naccarati [Italie] ; Marc Chadeau-Hyam [Royaume-Uni] ; Ugo Ala [Italie] ; Christian Faltus [Allemagne] ; Rudolf Kaaks [Allemagne] ; Angela Risch [Allemagne, Autriche] ; Bianca De Stavola [Royaume-Uni] ; Allison Hodge [Australie] ; Graham G. Giles [Australie] ; Melissa C. Southey [Australie] ; Caroline L. Relton [Royaume-Uni] ; Philip C. Haycock [Royaume-Uni] ; Eiliv Lund [Norvège] ; Silvia Polidoro [Italie] ; Torkjel M. Sandanger [Norvège] ; Gianluca Severi [Italie, France, Australie] ; Paolo Vineis [Italie, Royaume-Uni]Source :
- Nature Communications [ 2041-1723 ] ; 2015.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Tabagisme, Tumeurs du poumon.
- physiologie : Régulation de l'expression des gènes.
- Adulte, Adulte d'âge moyen, Femelle, Humains, Ilots CpG, Mâle, Odds ratio, Prédisposition génétique à une maladie, Sujet âgé, Études de cohortes.
English descriptors
- KwdEn :
- MESH :
- genetics : Lung Neoplasms, Smoking.
- physiology : Gene Expression Regulation.
- Adult, Aged, Cohort Studies, CpG Islands, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Odds Ratio.
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
Url:
DOI: 10.1038/ncomms10192
PubMed: 26667048
PubMed Central: 4682166
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PMC:4682166Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts</title>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Paris-South University</institution>
, Villejuif 91450,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ponzi, Erica" sort="Ponzi, Erica" uniqKey="Ponzi E" first="Erica" last="Ponzi">Erica Ponzi</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Guida, Florence" sort="Guida, Florence" uniqKey="Guida F" first="Florence" last="Guida">Florence Guida</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Genetic Epidemiology Division, International Agency for Research on Cancer</institution>
, Lyon 69008,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Biobank Research, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Biobank Research, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Johansson, Mikael" sort="Johansson, Mikael" uniqKey="Johansson M" first="Mikael" last="Johansson">Mikael Johansson</name>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>Department of Radiation Sciences, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Assumma, Manuela Bianca" sort="Assumma, Manuela Bianca" uniqKey="Assumma M" first="Manuela Bianca" last="Assumma">Manuela Bianca Assumma</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chadeau Hyam, Marc" sort="Chadeau Hyam, Marc" uniqKey="Chadeau Hyam M" first="Marc" last="Chadeau-Hyam">Marc Chadeau-Hyam</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Department of Molecular Biotechnology and Health Sciences, Università di Torino</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Faltus, Christian" sort="Faltus, Christian" uniqKey="Faltus C" first="Christian" last="Faltus">Christian Faltus</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Division of Epigenomics and Cancer Risk Factors, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Division of Cancer Epidemiology, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL)</institution>
, Heidelberg 69120,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Division of Epigenomics and Cancer Risk Factors, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL)</institution>
, Heidelberg 69120,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a15"><institution>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg</institution>
, Salzburg 5020,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="De Stavola, Bianca" sort="De Stavola, Bianca" uniqKey="De Stavola B" first="Bianca" last="De Stavola">Bianca De Stavola</name>
<affiliation wicri:level="1"><nlm:aff id="a16"><institution>Department of Medical Statistics, London School of Hygiene and Tropical Medicine</institution>
, London WC1E 7HT,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name>
<affiliation wicri:level="1"><nlm:aff id="a17"><institution>Genetic Epidemiology Laboratory, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L." last="Relton">Caroline L. Relton</name>
<affiliation wicri:level="1"><nlm:aff id="a18"><institution>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol</institution>
BS8 2BN,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haycock, Philip C" sort="Haycock, Philip C" uniqKey="Haycock P" first="Philip C." last="Haycock">Philip C. Haycock</name>
<affiliation wicri:level="1"><nlm:aff id="a18"><institution>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol</institution>
BS8 2BN,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lund, Eiliv" sort="Lund, Eiliv" uniqKey="Lund E" first="Eiliv" last="Lund">Eiliv Lund</name>
<affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Community Medicine UiT–The Arctic University of Norway</institution>
, Tromso 9019,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Polidoro, Silvia" sort="Polidoro, Silvia" uniqKey="Polidoro S" first="Silvia" last="Polidoro">Silvia Polidoro</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sandanger, Torkjel M" sort="Sandanger, Torkjel M" uniqKey="Sandanger T" first="Torkjel M." last="Sandanger">Torkjel M. Sandanger</name>
<affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Community Medicine UiT–The Arctic University of Norway</institution>
, Tromso 9019,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health</institution>
, U1018, Team 9, 114 rue Edouard Vaillant, Villejuif 94805,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Paris-South University</institution>
, Villejuif 91450,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Cohort Studies</term>
<term>CpG Islands</term>
<term>Female</term>
<term>Gene Expression Regulation (physiology)</term>
<term>Genetic Predisposition to Disease</term>
<term>Humans</term>
<term>Lung Neoplasms (genetics)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Odds Ratio</term>
<term>Smoking (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Humains</term>
<term>Ilots CpG</term>
<term>Mâle</term>
<term>Odds ratio</term>
<term>Prédisposition génétique à une maladie</term>
<term>Régulation de l'expression des gènes (physiologie)</term>
<term>Sujet âgé</term>
<term>Tabagisme (génétique)</term>
<term>Tumeurs du poumon (génétique)</term>
<term>Études de cohortes</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lung Neoplasms</term>
<term>Smoking</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Tabagisme</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Régulation de l'expression des gènes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Gene Expression Regulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Cohort Studies</term>
<term>CpG Islands</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Odds Ratio</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Humains</term>
<term>Ilots CpG</term>
<term>Mâle</term>
<term>Odds ratio</term>
<term>Prédisposition génétique à une maladie</term>
<term>Sujet âgé</term>
<term>Études de cohortes</term>
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<front><div type="abstract" xml:lang="en"><p>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 <italic>AHRR</italic>
(OR for 1 s.d.=0.37, 95% CI: 0.31–0.54, <italic>P</italic>
-value=3.3 × 10<sup>−11</sup>
) and cg03636183 in <italic>F2RL3</italic>
(OR for 1 s.d.=0.40, 95% CI: 0.31–0.56, <italic>P</italic>
-value=3.9 × 10<sup>−10</sup>
), 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.</p>
</div>
</front>
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</div1>
</back>
</TEI>
<double pmid="26667048"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts</title>
<author><name sortKey="Fasanelli, Francesca" sort="Fasanelli, Francesca" uniqKey="Fasanelli F" first="Francesca" last="Fasanelli">Francesca Fasanelli</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin, Center for Cancer Prevention</institution>
, Via Santena 7, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health</institution>
, U1018, Team 9, 114 rue Edouard Vaillant, Villejuif 94805,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Paris-South University</institution>
, Villejuif 91450,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ponzi, Erica" sort="Ponzi, Erica" uniqKey="Ponzi E" first="Erica" last="Ponzi">Erica Ponzi</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Guida, Florence" sort="Guida, Florence" uniqKey="Guida F" first="Florence" last="Guida">Florence Guida</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Genetic Epidemiology Division, International Agency for Research on Cancer</institution>
, Lyon 69008,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Biobank Research, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Biobank Research, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Johansson, Mikael" sort="Johansson, Mikael" uniqKey="Johansson M" first="Mikael" last="Johansson">Mikael Johansson</name>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>Department of Radiation Sciences, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Assumma, Manuela Bianca" sort="Assumma, Manuela Bianca" uniqKey="Assumma M" first="Manuela Bianca" last="Assumma">Manuela Bianca Assumma</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chadeau Hyam, Marc" sort="Chadeau Hyam, Marc" uniqKey="Chadeau Hyam M" first="Marc" last="Chadeau-Hyam">Marc Chadeau-Hyam</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Department of Molecular Biotechnology and Health Sciences, Università di Torino</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Faltus, Christian" sort="Faltus, Christian" uniqKey="Faltus C" first="Christian" last="Faltus">Christian Faltus</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Division of Epigenomics and Cancer Risk Factors, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Division of Cancer Epidemiology, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL)</institution>
, Heidelberg 69120,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Division of Epigenomics and Cancer Risk Factors, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL)</institution>
, Heidelberg 69120,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a15"><institution>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg</institution>
, Salzburg 5020,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="De Stavola, Bianca" sort="De Stavola, Bianca" uniqKey="De Stavola B" first="Bianca" last="De Stavola">Bianca De Stavola</name>
<affiliation wicri:level="1"><nlm:aff id="a16"><institution>Department of Medical Statistics, London School of Hygiene and Tropical Medicine</institution>
, London WC1E 7HT,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name>
<affiliation wicri:level="1"><nlm:aff id="a17"><institution>Genetic Epidemiology Laboratory, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L." last="Relton">Caroline L. Relton</name>
<affiliation wicri:level="1"><nlm:aff id="a18"><institution>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol</institution>
BS8 2BN,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haycock, Philip C" sort="Haycock, Philip C" uniqKey="Haycock P" first="Philip C." last="Haycock">Philip C. Haycock</name>
<affiliation wicri:level="1"><nlm:aff id="a18"><institution>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol</institution>
BS8 2BN,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lund, Eiliv" sort="Lund, Eiliv" uniqKey="Lund E" first="Eiliv" last="Lund">Eiliv Lund</name>
<affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Community Medicine UiT–The Arctic University of Norway</institution>
, Tromso 9019,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Polidoro, Silvia" sort="Polidoro, Silvia" uniqKey="Polidoro S" first="Silvia" last="Polidoro">Silvia Polidoro</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sandanger, Torkjel M" sort="Sandanger, Torkjel M" uniqKey="Sandanger T" first="Torkjel M." last="Sandanger">Torkjel M. Sandanger</name>
<affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Community Medicine UiT–The Arctic University of Norway</institution>
, Tromso 9019,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health</institution>
, U1018, Team 9, 114 rue Edouard Vaillant, Villejuif 94805,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Paris-South University</institution>
, Villejuif 91450,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26667048</idno>
<idno type="pmc">4682166</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682166</idno>
<idno type="RBID">PMC:4682166</idno>
<idno type="doi">10.1038/ncomms10192</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000749</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000749</idno>
<idno type="wicri:Area/Pmc/Curation">000748</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000748</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000F35</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000F35</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts</title>
<author><name sortKey="Fasanelli, Francesca" sort="Fasanelli, Francesca" uniqKey="Fasanelli F" first="Francesca" last="Fasanelli">Francesca Fasanelli</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a2"><institution>Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin, Center for Cancer Prevention</institution>
, Via Santena 7, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health</institution>
, U1018, Team 9, 114 rue Edouard Vaillant, Villejuif 94805,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Paris-South University</institution>
, Villejuif 91450,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ponzi, Erica" sort="Ponzi, Erica" uniqKey="Ponzi E" first="Erica" last="Ponzi">Erica Ponzi</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Guida, Florence" sort="Guida, Florence" uniqKey="Guida F" first="Florence" last="Guida">Florence Guida</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Genetic Epidemiology Division, International Agency for Research on Cancer</institution>
, Lyon 69008,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Biobank Research, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Biobank Research, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Johansson, Mikael" sort="Johansson, Mikael" uniqKey="Johansson M" first="Mikael" last="Johansson">Mikael Johansson</name>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>Department of Radiation Sciences, Umeå University</institution>
, Umeå SE—90187,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Assumma, Manuela Bianca" sort="Assumma, Manuela Bianca" uniqKey="Assumma M" first="Manuela Bianca" last="Assumma">Manuela Bianca Assumma</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chadeau Hyam, Marc" sort="Chadeau Hyam, Marc" uniqKey="Chadeau Hyam M" first="Marc" last="Chadeau-Hyam">Marc Chadeau-Hyam</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Department of Molecular Biotechnology and Health Sciences, Università di Torino</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Faltus, Christian" sort="Faltus, Christian" uniqKey="Faltus C" first="Christian" last="Faltus">Christian Faltus</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Division of Epigenomics and Cancer Risk Factors, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Division of Cancer Epidemiology, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL)</institution>
, Heidelberg 69120,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Division of Epigenomics and Cancer Risk Factors, DKFZ—German Cancer Research Center</institution>
, Heidelberg 69121,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL)</institution>
, Heidelberg 69120,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a15"><institution>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg</institution>
, Salzburg 5020,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="De Stavola, Bianca" sort="De Stavola, Bianca" uniqKey="De Stavola B" first="Bianca" last="De Stavola">Bianca De Stavola</name>
<affiliation wicri:level="1"><nlm:aff id="a16"><institution>Department of Medical Statistics, London School of Hygiene and Tropical Medicine</institution>
, London WC1E 7HT,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name>
<affiliation wicri:level="1"><nlm:aff id="a17"><institution>Genetic Epidemiology Laboratory, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L." last="Relton">Caroline L. Relton</name>
<affiliation wicri:level="1"><nlm:aff id="a18"><institution>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol</institution>
BS8 2BN,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haycock, Philip C" sort="Haycock, Philip C" uniqKey="Haycock P" first="Philip C." last="Haycock">Philip C. Haycock</name>
<affiliation wicri:level="1"><nlm:aff id="a18"><institution>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol</institution>
BS8 2BN,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lund, Eiliv" sort="Lund, Eiliv" uniqKey="Lund E" first="Eiliv" last="Lund">Eiliv Lund</name>
<affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Community Medicine UiT–The Arctic University of Norway</institution>
, Tromso 9019,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Polidoro, Silvia" sort="Polidoro, Silvia" uniqKey="Polidoro S" first="Silvia" last="Polidoro">Silvia Polidoro</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sandanger, Torkjel M" sort="Sandanger, Torkjel M" uniqKey="Sandanger T" first="Torkjel M." last="Sandanger">Torkjel M. Sandanger</name>
<affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Community Medicine UiT–The Arctic University of Norway</institution>
, Tromso 9019,<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health</institution>
, U1018, Team 9, 114 rue Edouard Vaillant, Villejuif 94805,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Paris-South University</institution>
, Villejuif 91450,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria</institution>
, Melbourne, Victoria 3004,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne</institution>
, Melbourne, Victoria 3010,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation</institution>
, Torino 10126,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place</institution>
, London W2 1PG,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>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 <italic>AHRR</italic>
(OR for 1 s.d.=0.37, 95% CI: 0.31–0.54, <italic>P</italic>
-value=3.3 × 10<sup>−11</sup>
) and cg03636183 in <italic>F2RL3</italic>
(OR for 1 s.d.=0.40, 95% CI: 0.31–0.56, <italic>P</italic>
-value=3.9 × 10<sup>−10</sup>
), 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.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Monick, M M" uniqKey="Monick M">M. M. Monick</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Elliott, H R" uniqKey="Elliott H">H. R. Elliott</name>
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</analytic>
</biblStruct>
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</biblStruct>
<biblStruct><analytic><author><name sortKey="Zeilinger, S" uniqKey="Zeilinger S">S. Zeilinger</name>
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</analytic>
</biblStruct>
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<biblStruct><analytic><author><name sortKey="Shenker, N S" uniqKey="Shenker N">N. S. Shenker</name>
</author>
</analytic>
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<author><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name>
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<author><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name>
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<author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G" last="Giles">Graham G. Giles</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts.</title>
<author><name sortKey="Fasanelli, Francesca" sort="Fasanelli, Francesca" uniqKey="Fasanelli F" first="Francesca" last="Fasanelli">Francesca Fasanelli</name>
<affiliation wicri:level="1"><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name>
<affiliation wicri:level="1"><nlm:affiliation>Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health, U1018, Team 9, 114 rue Edouard Vaillant, Villejuif 94805, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health, U1018, Team 9, 114 rue Edouard Vaillant, Villejuif 94805</wicri:regionArea>
<wicri:noRegion>94805</wicri:noRegion>
<wicri:noRegion>94805</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ponzi, Erica" sort="Ponzi, Erica" uniqKey="Ponzi E" first="Erica" last="Ponzi">Erica Ponzi</name>
<affiliation wicri:level="1"><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Guida, Florence" sort="Guida, Florence" uniqKey="Guida F" first="Florence" last="Guida">Florence Guida</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG</wicri:regionArea>
<wicri:noRegion>London W2 1PG</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG</wicri:regionArea>
<wicri:noRegion>London W2 1PG</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name>
<affiliation wicri:level="1"><nlm:affiliation>Genetic Epidemiology Division, International Agency for Research on Cancer, Lyon 69008, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Genetic Epidemiology Division, International Agency for Research on Cancer, Lyon 69008</wicri:regionArea>
<wicri:noRegion>69008</wicri:noRegion>
<placeName><settlement type="city">Lyon</settlement>
<region type="region" nuts="2">Auvergne-Rhône-Alpes</region>
<region type="old region" nuts="2">Rhône-Alpes</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biobank Research, Umeå University, Umeå SE-90187, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Biobank Research, Umeå University, Umeå SE-90187</wicri:regionArea>
<wicri:noRegion>Umeå SE-90187</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Johansson, Mikael" sort="Johansson, Mikael" uniqKey="Johansson M" first="Mikael" last="Johansson">Mikael Johansson</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Radiation Sciences, Umeå University, Umeå SE-90187, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Radiation Sciences, Umeå University, Umeå SE-90187</wicri:regionArea>
<wicri:noRegion>Umeå SE-90187</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Assumma, Manuela Bianca" sort="Assumma, Manuela Bianca" uniqKey="Assumma M" first="Manuela Bianca" last="Assumma">Manuela Bianca Assumma</name>
<affiliation wicri:level="1"><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name>
<affiliation wicri:level="1"><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chadeau Hyam, Marc" sort="Chadeau Hyam, Marc" uniqKey="Chadeau Hyam M" first="Marc" last="Chadeau-Hyam">Marc Chadeau-Hyam</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG</wicri:regionArea>
<wicri:noRegion>London W2 1PG</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Molecular Biotechnology and Health Sciences, Università di Torino, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Faltus, Christian" sort="Faltus, Christian" uniqKey="Faltus C" first="Christian" last="Faltus">Christian Faltus</name>
<affiliation wicri:level="3"><nlm:affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name>
<affiliation wicri:level="3"><nlm:affiliation>Division of Cancer Epidemiology, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Cancer Epidemiology, DKFZ-German Cancer Research Center, Heidelberg 69121</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name>
<affiliation wicri:level="3"><nlm:affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Stavola, Bianca" sort="De Stavola, Bianca" uniqKey="De Stavola B" first="Bianca" last="De Stavola">Bianca De Stavola</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London WC1E 7HT</wicri:regionArea>
<wicri:noRegion>London WC1E 7HT</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004</wicri:regionArea>
<wicri:noRegion>Victoria 3004</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G" last="Giles">Graham G. Giles</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004</wicri:regionArea>
<wicri:noRegion>Victoria 3004</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C" last="Southey">Melissa C. Southey</name>
<affiliation wicri:level="4"><nlm:affiliation>Genetic Epidemiology Laboratory, University of Melbourne, Melbourne, Victoria 3010, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Genetic Epidemiology Laboratory, University of Melbourne, Melbourne, Victoria 3010</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L" last="Relton">Caroline L. Relton</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN</wicri:regionArea>
<wicri:noRegion>Bristol BS8 2BN</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Haycock, Philip C" sort="Haycock, Philip C" uniqKey="Haycock P" first="Philip C" last="Haycock">Philip C. Haycock</name>
<affiliation wicri:level="1"><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN</wicri:regionArea>
<wicri:noRegion>Bristol BS8 2BN</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lund, Eiliv" sort="Lund, Eiliv" uniqKey="Lund E" first="Eiliv" last="Lund">Eiliv Lund</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</nlm:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019</wicri:regionArea>
<wicri:noRegion>Tromso 9019</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Polidoro, Silvia" sort="Polidoro, Silvia" uniqKey="Polidoro S" first="Silvia" last="Polidoro">Silvia Polidoro</name>
<affiliation wicri:level="1"><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sandanger, Torkjel M" sort="Sandanger, Torkjel M" uniqKey="Sandanger T" first="Torkjel M" last="Sandanger">Torkjel M. Sandanger</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</nlm:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019</wicri:regionArea>
<wicri:noRegion>Tromso 9019</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation wicri:level="1"><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name>
<affiliation wicri:level="1"><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126</wicri:regionArea>
<placeName><settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
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</analytic>
<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2015" type="published">2015</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Cohort Studies</term>
<term>CpG Islands</term>
<term>Female</term>
<term>Gene Expression Regulation (physiology)</term>
<term>Genetic Predisposition to Disease</term>
<term>Humans</term>
<term>Lung Neoplasms (genetics)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Odds Ratio</term>
<term>Smoking (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Humains</term>
<term>Ilots CpG</term>
<term>Mâle</term>
<term>Odds ratio</term>
<term>Prédisposition génétique à une maladie</term>
<term>Régulation de l'expression des gènes (physiologie)</term>
<term>Sujet âgé</term>
<term>Tabagisme (génétique)</term>
<term>Tumeurs du poumon (génétique)</term>
<term>Études de cohortes</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lung Neoplasms</term>
<term>Smoking</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Tabagisme</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Régulation de l'expression des gènes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Gene Expression Regulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Cohort Studies</term>
<term>CpG Islands</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Odds Ratio</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Humains</term>
<term>Ilots CpG</term>
<term>Mâle</term>
<term>Odds ratio</term>
<term>Prédisposition génétique à une maladie</term>
<term>Sujet âgé</term>
<term>Études de cohortes</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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