Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts.
Identifieur interne : 002644 ( PubMed/Corpus ); précédent : 002643; suivant : 002645Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts.
Auteurs : Francesca Fasanelli ; Laura Baglietto ; Erica Ponzi ; Florence Guida ; Gianluca Campanella ; Mattias Johansson ; Kjell Grankvist ; Mikael Johansson ; Manuela Bianca Assumma ; Alessio Naccarati ; Marc Chadeau-Hyam ; Ugo Ala ; Christian Faltus ; Rudolf Kaaks ; Angela Risch ; Bianca De Stavola ; Allison Hodge ; Graham G. Giles ; Melissa C. Southey ; Caroline L. Relton ; Philip C. Haycock ; Eiliv Lund ; Silvia Polidoro ; Torkjel M. Sandanger ; Gianluca Severi ; Paolo VineisSource :
- Nature communications [ 2041-1723 ] ; 2015.
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 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.
DOI: 10.1038/ncomms10192
PubMed: 26667048
Links to Exploration step
pubmed:26667048Le document en format XML
<record><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><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name><affiliation><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></affiliation></author><author><name sortKey="Ponzi, Erica" sort="Ponzi, Erica" uniqKey="Ponzi E" first="Erica" last="Ponzi">Erica Ponzi</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Guida, Florence" sort="Guida, Florence" uniqKey="Guida F" first="Florence" last="Guida">Florence Guida</name><affiliation><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></affiliation></author><author><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name><affiliation><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></affiliation></author><author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name><affiliation><nlm:affiliation>Genetic Epidemiology Division, International Agency for Research on Cancer, Lyon 69008, France.</nlm:affiliation></affiliation></author><author><name sortKey="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name><affiliation><nlm:affiliation>Department of Biobank Research, Umeå University, Umeå SE-90187, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Johansson, Mikael" sort="Johansson, Mikael" uniqKey="Johansson M" first="Mikael" last="Johansson">Mikael Johansson</name><affiliation><nlm:affiliation>Department of Radiation Sciences, Umeå University, Umeå SE-90187, Sweden.</nlm:affiliation></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><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name><affiliation><nlm:affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Faltus, Christian" sort="Faltus, Christian" uniqKey="Faltus C" first="Christian" last="Faltus">Christian Faltus</name><affiliation><nlm:affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name><affiliation><nlm:affiliation>Division of Cancer Epidemiology, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name><affiliation><nlm:affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation></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><nlm:affiliation>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name><affiliation><nlm:affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</nlm:affiliation></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><nlm:affiliation>Genetic Epidemiology Laboratory, University of Melbourne, Melbourne, Victoria 3010, Australia.</nlm:affiliation></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><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</nlm:affiliation></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><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Lund, Eiliv" sort="Lund, Eiliv" uniqKey="Lund E" first="Eiliv" last="Lund">Eiliv Lund</name><affiliation><nlm:affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Polidoro, Silvia" sort="Polidoro, Silvia" uniqKey="Polidoro S" first="Silvia" last="Polidoro">Silvia Polidoro</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></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><nlm:affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26667048</idno><idno type="pmid">26667048</idno><idno type="doi">10.1038/ncomms10192</idno><idno type="wicri:Area/PubMed/Corpus">002644</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002644</idno></publicationStmt><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><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name><affiliation><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></affiliation></author><author><name sortKey="Ponzi, Erica" sort="Ponzi, Erica" uniqKey="Ponzi E" first="Erica" last="Ponzi">Erica Ponzi</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Guida, Florence" sort="Guida, Florence" uniqKey="Guida F" first="Florence" last="Guida">Florence Guida</name><affiliation><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></affiliation></author><author><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name><affiliation><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></affiliation></author><author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name><affiliation><nlm:affiliation>Genetic Epidemiology Division, International Agency for Research on Cancer, Lyon 69008, France.</nlm:affiliation></affiliation></author><author><name sortKey="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name><affiliation><nlm:affiliation>Department of Biobank Research, Umeå University, Umeå SE-90187, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Johansson, Mikael" sort="Johansson, Mikael" uniqKey="Johansson M" first="Mikael" last="Johansson">Mikael Johansson</name><affiliation><nlm:affiliation>Department of Radiation Sciences, Umeå University, Umeå SE-90187, Sweden.</nlm:affiliation></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><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name><affiliation><nlm:affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Faltus, Christian" sort="Faltus, Christian" uniqKey="Faltus C" first="Christian" last="Faltus">Christian Faltus</name><affiliation><nlm:affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name><affiliation><nlm:affiliation>Division of Cancer Epidemiology, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name><affiliation><nlm:affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</nlm:affiliation></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><nlm:affiliation>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name><affiliation><nlm:affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</nlm:affiliation></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><nlm:affiliation>Genetic Epidemiology Laboratory, University of Melbourne, Melbourne, Victoria 3010, Australia.</nlm:affiliation></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><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</nlm:affiliation></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><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Lund, Eiliv" sort="Lund, Eiliv" uniqKey="Lund E" first="Eiliv" last="Lund">Eiliv Lund</name><affiliation><nlm:affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Polidoro, Silvia" sort="Polidoro, Silvia" uniqKey="Polidoro S" first="Silvia" last="Polidoro">Silvia Polidoro</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></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><nlm:affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name><affiliation><nlm:affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><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="MESH" qualifier="genetics" xml:lang="en"><term>Lung Neoplasms</term><term>Smoking</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></textClass></profileDesc></teiHeader><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></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26667048</PMID><DateCreated><Year>2015</Year><Month>12</Month><Day>15</Day></DateCreated><DateCompleted><Year>2016</Year><Month>05</Month><Day>31</Day></DateCompleted><DateRevised><Year>2017</Year><Month>11</Month><Day>10</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN><JournalIssue CitedMedium="Internet"><Volume>6</Volume><PubDate><Year>2015</Year><Month>Dec</Month><Day>15</Day></PubDate></JournalIssue><Title>Nature communications</Title><ISOAbbreviation>Nat Commun</ISOAbbreviation></Journal><ArticleTitle>Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts.</ArticleTitle><Pagination><MedlinePgn>10192</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/ncomms10192</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fasanelli</LastName><ForeName>Francesca</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin, Center for Cancer Prevention, Via Santena 7, Torino 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baglietto</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Paris-South University, Villejuif 91450, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ponzi</LastName><ForeName>Erica</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guida</LastName><ForeName>Florence</ForeName><Initials>F</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Campanella</LastName><ForeName>Gianluca</ForeName><Initials>G</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-5411-6338</Identifier><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansson</LastName><ForeName>Mattias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Genetic Epidemiology Division, International Agency for Research on Cancer, Lyon 69008, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biobank Research, Umeå University, Umeå SE-90187, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grankvist</LastName><ForeName>Kjell</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Biobank Research, Umeå University, Umeå SE-90187, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansson</LastName><ForeName>Mikael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Radiation Sciences, Umeå University, Umeå SE-90187, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Assumma</LastName><ForeName>Manuela Bianca</ForeName><Initials>MB</Initials><AffiliationInfo><Affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Naccarati</LastName><ForeName>Alessio</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chadeau-Hyam</LastName><ForeName>Marc</ForeName><Initials>M</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ala</LastName><ForeName>Ugo</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, Torino 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Faltus</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kaaks</LastName><ForeName>Rudolf</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Cancer Epidemiology, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg 69120, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Risch</LastName><ForeName>Angela</ForeName><Initials>A</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-8026-5505</Identifier><AffiliationInfo><Affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg 69121, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg 69120, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg 5020, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>De Stavola</LastName><ForeName>Bianca</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hodge</LastName><ForeName>Allison</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giles</LastName><ForeName>Graham G</ForeName><Initials>GG</Initials><AffiliationInfo><Affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Southey</LastName><ForeName>Melissa C</ForeName><Initials>MC</Initials><AffiliationInfo><Affiliation>Genetic Epidemiology Laboratory, University of Melbourne, Melbourne, Victoria 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Relton</LastName><ForeName>Caroline L</ForeName><Initials>CL</Initials><AffiliationInfo><Affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haycock</LastName><ForeName>Philip C</ForeName><Initials>PC</Initials><AffiliationInfo><Affiliation>MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lund</LastName><ForeName>Eiliv</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Polidoro</LastName><ForeName>Silvia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sandanger</LastName><ForeName>Torkjel M</ForeName><Initials>TM</Initials><AffiliationInfo><Affiliation>Department of Community Medicine UiT-The Arctic University of Norway, Tromso 9019, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Severi</LastName><ForeName>Gianluca</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><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.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Paris-South University, Villejuif 91450, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Genetic Epidemiology, Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria 3004, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vineis</LastName><ForeName>Paolo</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino 10126, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>A19169</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MC_UU_12013/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MC_UU_12013/2</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>12</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Commun</MedlineTA><NlmUniqueID>101528555</NlmUniqueID><ISSNLinking>2041-1723</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>BMC Biotechnol. 2013;13:23</RefSource><PMID Version="1">23497093</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Intern Med. 2011 Jun 7;154(11):719-26</RefSource><PMID Version="1">21646555</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Mol Genet. 2013 Mar 1;22(5):843-51</RefSource><PMID 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Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016017" MajorTopicYN="N">Odds Ratio</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012907" MajorTopicYN="N">Smoking</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4682166</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>02</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>12</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>12</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>6</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26667048</ArticleId><ArticleId IdType="pii">ncomms10192</ArticleId><ArticleId IdType="doi">10.1038/ncomms10192</ArticleId><ArticleId IdType="pmc">PMC4682166</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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