DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk.
Identifieur interne : 000E80 ( Main/Exploration ); précédent : 000E79; suivant : 000E81DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk.
Auteurs : Laura Baglietto [France] ; Erica Ponzi [Suisse] ; Philip Haycock [Royaume-Uni] ; Allison Hodge [Australie] ; Manuela Bianca Assumma [Italie] ; Chol-Hee Jung [Australie] ; Jessica Chung [Australie] ; Francesca Fasanelli [Italie] ; Florence Guida [Royaume-Uni] ; Gianluca Campanella [Royaume-Uni] ; Marc Chadeau-Hyam [Royaume-Uni] ; Kjell Grankvist [Suède] ; Mikael Johansson [Suède] ; Ugo Ala [Italie] ; Paolo Provero [Italie] ; Ee Ming Wong [Australie] ; Jihoon Joo [Australie] ; Dallas R. English [Australie] ; Nabila Kazmi [Royaume-Uni] ; Eiliv Lund [Norvège] ; Christian Faltus [Autriche] ; Rudolf Kaaks [Allemagne] ; Angela Risch [Autriche] ; Myrto Barrdahl [Allemagne] ; Torkjel M. Sandanger [Norvège] ; Melissa C. Southey [Australie] ; Graham G. Giles [Australie] ; Mattias Johansson [France] ; Paolo Vineis [Italie] ; Silvia Polidoro [Italie] ; Caroline L. Relton [Royaume-Uni] ; Gianluca Severi [France]Source :
- International journal of cancer [ 1097-0215 ] ; 2017.
Descripteurs français
- KwdFr :
- ADN (sang), Analyse sur microréseau (), Détection précoce de cancer, Femelle, Humains, Mâle, Méthylation de l'ADN, Prédisposition génétique à une maladie, Tabagisme (effets indésirables), Tabagisme (génétique), Tumeurs du poumon (), Tumeurs du poumon (diagnostic), Tumeurs du poumon (génétique), Épigenèse génétique, Études cas-témoins.
- MESH :
- diagnostic : Tumeurs du poumon.
- effets indésirables : Tabagisme.
- génétique : Tabagisme, Tumeurs du poumon.
- sang : ADN.
- Analyse sur microréseau, Détection précoce de cancer, Femelle, Humains, Mâle, Méthylation de l'ADN, Prédisposition génétique à une maladie, Tumeurs du poumon, Épigenèse génétique, Études cas-témoins.
English descriptors
- KwdEn :
- Case-Control Studies, DNA (blood), DNA Methylation, Early Detection of Cancer, Epigenesis, Genetic, Female, Genetic Predisposition to Disease, Humans, Lung Neoplasms (chemically induced), Lung Neoplasms (diagnosis), Lung Neoplasms (genetics), Male, Microarray Analysis (methods), Smoking (adverse effects), Smoking (genetics).
- MESH :
- chemical , blood : DNA.
- adverse effects : Smoking.
- chemically induced : Lung Neoplasms.
- diagnosis : Lung Neoplasms.
- genetics : Lung Neoplasms, Smoking.
- methods : Microarray Analysis.
- Case-Control Studies, DNA Methylation, Early Detection of Cancer, Epigenesis, Genetic, Female, Genetic Predisposition to Disease, Humans, Male.
Abstract
DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled = 4 × 10(-17) ), cg03636183 in the F2RL3 gene (p-valuepooled = 2 × 10 (- 13) ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled = 7 × 10(-16) and 1 × 10(-11) respectively), cg06126421 in 6p21.33 (p-valuepooled = 2 × 10(-15) ) and cg23387569 in 12q14.1 (p-valuepooled = 5 × 10(-7) ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity ≤ 1.8 x10 (- 7) ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.
DOI: 10.1002/ijc.30431
PubMed: 27632354
Affiliations:
- Allemagne, Australie, Autriche, France, Italie, Norvège, Royaume-Uni, Suisse, Suède
- Auvergne-Rhône-Alpes, Bade-Wurtemberg, Canton de Zurich, District de Karlsruhe, Rhône-Alpes, Victoria (État)
- Heidelberg, Lyon, Melbourne, Zurich
- Université de Melbourne, Université de Zurich
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Le document en format XML
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English</name><affiliation wicri:level="3"><nlm:affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Kazmi, Nabila" sort="Kazmi, Nabila" uniqKey="Kazmi N" first="Nabila" last="Kazmi">Nabila Kazmi</name><affiliation wicri:level="1"><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN</wicri:regionArea><wicri:noRegion>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, Norway.</nlm:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Community Medicine, UiT- The Arctic University of Norway, Tromso</wicri:regionArea><wicri:noRegion>Tromso</wicri:noRegion></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:affiliation>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg</wicri:regionArea><wicri:noRegion>Salzburg</wicri:noRegion></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, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg</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="1"><nlm:affiliation>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg</wicri:regionArea><wicri:noRegion>Salzburg</wicri:noRegion></affiliation></author><author><name sortKey="Barrdahl, Myrto" sort="Barrdahl, Myrto" uniqKey="Barrdahl M" first="Myrto" last="Barrdahl">Myrto Barrdahl</name><affiliation wicri:level="3"><nlm:affiliation>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg</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="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, Norway.</nlm:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Community Medicine, UiT- The Arctic University of Norway, Tromso</wicri:regionArea><wicri:noRegion>Tromso</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, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></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="3"><nlm:affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name><affiliation wicri:level="3"><nlm:affiliation>International Agency for Research on Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>International Agency for Research on Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>HuGeF, Human Genetics Foundation, Torino, 10126</wicri:regionArea><wicri:noRegion>10126</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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>HuGeF, Human Genetics Foundation, Torino, 10126</wicri:regionArea><wicri:noRegion>10126</wicri:noRegion></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 & Community Medicine, University of Bristol, BS8 2BN, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN</wicri:regionArea><wicri:noRegion>BS8 2BN</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>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Saclay, Univ. 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Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</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="4"><nlm:affiliation>Department of Evolutionary Biology and Environmental Studies, University of Zurich, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Evolutionary Biology and Environmental Studies, University of Zurich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName><orgName type="university">Université de Zurich</orgName></affiliation></author><author><name sortKey="Haycock, Philip" sort="Haycock, Philip" uniqKey="Haycock P" first="Philip" last="Haycock">Philip Haycock</name><affiliation wicri:level="1"><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN</wicri:regionArea><wicri:noRegion>BS8 2BN</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="4"><nlm:affiliation>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Bianca Assumma, Manuela" sort="Bianca Assumma, Manuela" uniqKey="Bianca Assumma M" first="Manuela" last="Bianca Assumma">Manuela Bianca Assumma</name><affiliation wicri:level="1"><nlm:affiliation>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>HuGeF, Human Genetics Foundation, Torino, 10126</wicri:regionArea><wicri:noRegion>10126</wicri:noRegion></affiliation></author><author><name sortKey="Jung, Chol Hee" sort="Jung, Chol Hee" uniqKey="Jung C" first="Chol-Hee" last="Jung">Chol-Hee Jung</name><affiliation wicri:level="4"><nlm:affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Victorian Life Sciences Computation Initiative, The University of 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="Chung, Jessica" sort="Chung, Jessica" uniqKey="Chung J" first="Jessica" last="Chung">Jessica Chung</name><affiliation wicri:level="4"><nlm:affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Victorian Life Sciences Computation Initiative, The University of 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="Fasanelli, Francesca" sort="Fasanelli, Francesca" uniqKey="Fasanelli F" first="Francesca" last="Fasanelli">Francesca Fasanelli</name><affiliation wicri:level="1"><nlm:affiliation>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>HuGeF, Human Genetics Foundation, Torino, 10126</wicri:regionArea><wicri:noRegion>10126</wicri:noRegion></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>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>W2 1PG</wicri:noRegion></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>W2 1PG</wicri:noRegion></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, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Biobank Research, Umeå University</wicri:regionArea><wicri:noRegion>Umeå University</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, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Radiation Sciences, Umeå University</wicri:regionArea><wicri:noRegion>Umeå University</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, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10126</wicri:regionArea><wicri:noRegion>10126</wicri:noRegion></affiliation></author><author><name sortKey="Provero, Paolo" sort="Provero, Paolo" uniqKey="Provero P" first="Paolo" last="Provero">Paolo Provero</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10126</wicri:regionArea><wicri:noRegion>10126</wicri:noRegion></affiliation></author><author><name sortKey="Wong, Ee Ming" sort="Wong, Ee Ming" uniqKey="Wong E" first="Ee Ming" last="Wong">Ee Ming Wong</name><affiliation wicri:level="4"><nlm:affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Joo, Jihoon" sort="Joo, Jihoon" uniqKey="Joo J" first="Jihoon" last="Joo">Jihoon Joo</name><affiliation wicri:level="4"><nlm:affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="English, Dallas R" sort="English, Dallas R" uniqKey="English D" first="Dallas R" last="English">Dallas R. English</name><affiliation wicri:level="3"><nlm:affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Kazmi, Nabila" sort="Kazmi, Nabila" uniqKey="Kazmi N" first="Nabila" last="Kazmi">Nabila Kazmi</name><affiliation wicri:level="1"><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN</wicri:regionArea><wicri:noRegion>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, Norway.</nlm:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Community Medicine, UiT- The Arctic University of Norway, Tromso</wicri:regionArea><wicri:noRegion>Tromso</wicri:noRegion></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:affiliation>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg</wicri:regionArea><wicri:noRegion>Salzburg</wicri:noRegion></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, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg</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="1"><nlm:affiliation>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg</wicri:regionArea><wicri:noRegion>Salzburg</wicri:noRegion></affiliation></author><author><name sortKey="Barrdahl, Myrto" sort="Barrdahl, Myrto" uniqKey="Barrdahl M" first="Myrto" last="Barrdahl">Myrto Barrdahl</name><affiliation wicri:level="3"><nlm:affiliation>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg</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="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, Norway.</nlm:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Community Medicine, UiT- The Arctic University of Norway, Tromso</wicri:regionArea><wicri:noRegion>Tromso</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, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></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="3"><nlm:affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name><affiliation wicri:level="3"><nlm:affiliation>International Agency for Research on Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>International Agency for Research on Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>HuGeF, Human Genetics Foundation, Torino, 10126</wicri:regionArea><wicri:noRegion>10126</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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>HuGeF, Human Genetics Foundation, Torino, 10126</wicri:regionArea><wicri:noRegion>10126</wicri:noRegion></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 & Community Medicine, University of Bristol, BS8 2BN, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN</wicri:regionArea><wicri:noRegion>BS8 2BN</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>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of cancer</title><idno type="eISSN">1097-0215</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Case-Control Studies</term><term>DNA (blood)</term><term>DNA Methylation</term><term>Early Detection of Cancer</term><term>Epigenesis, Genetic</term><term>Female</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>Lung Neoplasms (chemically induced)</term><term>Lung Neoplasms (diagnosis)</term><term>Lung Neoplasms (genetics)</term><term>Male</term><term>Microarray Analysis (methods)</term><term>Smoking (adverse effects)</term><term>Smoking (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (sang)</term><term>Analyse sur microréseau ()</term><term>Détection précoce de cancer</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Méthylation de l'ADN</term><term>Prédisposition génétique à une maladie</term><term>Tabagisme (effets indésirables)</term><term>Tabagisme (génétique)</term><term>Tumeurs du poumon ()</term><term>Tumeurs du poumon (diagnostic)</term><term>Tumeurs du poumon (génétique)</term><term>Épigenèse génétique</term><term>Études cas-témoins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>DNA</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Smoking</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Tabagisme</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="methods" xml:lang="en"><term>Microarray Analysis</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>ADN</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Case-Control Studies</term><term>DNA Methylation</term><term>Early Detection of Cancer</term><term>Epigenesis, Genetic</term><term>Female</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>Male</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse sur microréseau</term><term>Détection précoce de cancer</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Méthylation de l'ADN</term><term>Prédisposition génétique à une maladie</term><term>Tumeurs du poumon</term><term>Épigenèse génétique</term><term>Études cas-témoins</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled = 4 × 10(-17) ), cg03636183 in the F2RL3 gene (p-valuepooled = 2 × 10 (- 13) ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled = 7 × 10(-16) and 1 × 10(-11) respectively), cg06126421 in 6p21.33 (p-valuepooled = 2 × 10(-15) ) and cg23387569 in 12q14.1 (p-valuepooled = 5 × 10(-7) ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity ≤ 1.8 x10 (- 7) ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Autriche</li><li>France</li><li>Italie</li><li>Norvège</li><li>Royaume-Uni</li><li>Suisse</li><li>Suède</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Bade-Wurtemberg</li><li>Canton de Zurich</li><li>District de Karlsruhe</li><li>Rhône-Alpes</li><li>Victoria (État)</li></region><settlement><li>Heidelberg</li><li>Lyon</li><li>Melbourne</li><li>Zurich</li></settlement><orgName><li>Université de Melbourne</li><li>Université de Zurich</li></orgName></list><tree><country name="France"><noRegion><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name></noRegion><name sortKey="Johansson, Mattias" sort="Johansson, Mattias" uniqKey="Johansson M" first="Mattias" last="Johansson">Mattias Johansson</name><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name></country><country name="Suisse"><region name="Canton de Zurich"><name sortKey="Ponzi, Erica" sort="Ponzi, Erica" uniqKey="Ponzi E" first="Erica" last="Ponzi">Erica Ponzi</name></region></country><country name="Royaume-Uni"><noRegion><name sortKey="Haycock, Philip" sort="Haycock, Philip" uniqKey="Haycock P" first="Philip" last="Haycock">Philip Haycock</name></noRegion><name sortKey="Campanella, Gianluca" sort="Campanella, Gianluca" uniqKey="Campanella G" first="Gianluca" last="Campanella">Gianluca Campanella</name><name sortKey="Chadeau Hyam, Marc" sort="Chadeau Hyam, Marc" uniqKey="Chadeau Hyam M" first="Marc" last="Chadeau-Hyam">Marc Chadeau-Hyam</name><name sortKey="Guida, Florence" sort="Guida, Florence" uniqKey="Guida F" first="Florence" last="Guida">Florence Guida</name><name sortKey="Kazmi, Nabila" sort="Kazmi, Nabila" uniqKey="Kazmi N" first="Nabila" last="Kazmi">Nabila Kazmi</name><name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L" last="Relton">Caroline L. Relton</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Hodge, Allison" sort="Hodge, Allison" uniqKey="Hodge A" first="Allison" last="Hodge">Allison Hodge</name></region><name sortKey="Chung, Jessica" sort="Chung, Jessica" uniqKey="Chung J" first="Jessica" last="Chung">Jessica Chung</name><name sortKey="English, Dallas R" sort="English, Dallas R" uniqKey="English D" first="Dallas R" last="English">Dallas R. English</name><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G" last="Giles">Graham G. Giles</name><name sortKey="Joo, Jihoon" sort="Joo, Jihoon" uniqKey="Joo J" first="Jihoon" last="Joo">Jihoon Joo</name><name sortKey="Jung, Chol Hee" sort="Jung, Chol Hee" uniqKey="Jung C" first="Chol-Hee" last="Jung">Chol-Hee Jung</name><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C" last="Southey">Melissa C. Southey</name><name sortKey="Wong, Ee Ming" sort="Wong, Ee Ming" uniqKey="Wong E" first="Ee Ming" last="Wong">Ee Ming Wong</name></country><country name="Italie"><noRegion><name sortKey="Bianca Assumma, Manuela" sort="Bianca Assumma, Manuela" uniqKey="Bianca Assumma M" first="Manuela" last="Bianca Assumma">Manuela Bianca Assumma</name></noRegion><name sortKey="Ala, Ugo" sort="Ala, Ugo" uniqKey="Ala U" first="Ugo" last="Ala">Ugo Ala</name><name sortKey="Fasanelli, Francesca" sort="Fasanelli, Francesca" uniqKey="Fasanelli F" first="Francesca" last="Fasanelli">Francesca Fasanelli</name><name sortKey="Polidoro, Silvia" sort="Polidoro, Silvia" uniqKey="Polidoro S" first="Silvia" last="Polidoro">Silvia Polidoro</name><name sortKey="Provero, Paolo" sort="Provero, Paolo" uniqKey="Provero P" first="Paolo" last="Provero">Paolo Provero</name><name sortKey="Vineis, Paolo" sort="Vineis, Paolo" uniqKey="Vineis P" first="Paolo" last="Vineis">Paolo Vineis</name></country><country name="Suède"><noRegion><name sortKey="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name></noRegion><name sortKey="Johansson, Mikael" sort="Johansson, Mikael" uniqKey="Johansson M" first="Mikael" last="Johansson">Mikael Johansson</name></country><country name="Norvège"><noRegion><name sortKey="Lund, Eiliv" sort="Lund, Eiliv" uniqKey="Lund E" first="Eiliv" last="Lund">Eiliv Lund</name></noRegion><name sortKey="Sandanger, Torkjel M" sort="Sandanger, Torkjel M" uniqKey="Sandanger T" first="Torkjel M" last="Sandanger">Torkjel M. Sandanger</name></country><country name="Autriche"><noRegion><name sortKey="Faltus, Christian" sort="Faltus, Christian" uniqKey="Faltus C" first="Christian" last="Faltus">Christian Faltus</name></noRegion><name sortKey="Risch, Angela" sort="Risch, Angela" uniqKey="Risch A" first="Angela" last="Risch">Angela Risch</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name></region><name sortKey="Barrdahl, Myrto" sort="Barrdahl, Myrto" uniqKey="Barrdahl M" first="Myrto" last="Barrdahl">Myrto Barrdahl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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