DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk.
Identifieur interne : 001377 ( PubMed/Corpus ); précédent : 001376; suivant : 001378DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk.
Auteurs : Laura Baglietto ; Erica Ponzi ; Philip Haycock ; Allison Hodge ; Manuela Bianca Assumma ; Chol-Hee Jung ; Jessica Chung ; Francesca Fasanelli ; Florence Guida ; Gianluca Campanella ; Marc Chadeau-Hyam ; Kjell Grankvist ; Mikael Johansson ; Ugo Ala ; Paolo Provero ; Ee Ming Wong ; Jihoon Joo ; Dallas R. English ; Nabila Kazmi ; Eiliv Lund ; Christian Faltus ; Rudolf Kaaks ; Angela Risch ; Myrto Barrdahl ; Torkjel M. Sandanger ; Melissa C. Southey ; Graham G. Giles ; Mattias Johansson ; Paolo Vineis ; Silvia Polidoro ; Caroline L. Relton ; Gianluca SeveriSource :
- International journal of cancer [ 1097-0215 ] ; 2017.
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
Links to Exploration step
pubmed:27632354Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk.</title><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name><affiliation><nlm:affiliation>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, 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>Department of Evolutionary Biology and Environmental Studies, University of Zurich, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Haycock, Philip" sort="Haycock, Philip" uniqKey="Haycock P" first="Philip" last="Haycock">Philip Haycock</name><affiliation><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN, 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>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</nlm:affiliation></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><nlm:affiliation>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation></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><nlm:affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Chung, Jessica" sort="Chung, Jessica" uniqKey="Chung J" first="Jessica" last="Chung">Jessica Chung</name><affiliation><nlm:affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Fasanelli, Francesca" sort="Fasanelli, Francesca" uniqKey="Fasanelli F" first="Francesca" last="Fasanelli">Francesca Fasanelli</name><affiliation><nlm:affiliation>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="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="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name><affiliation><nlm:affiliation>Department of Biobank Research, Umeå University, 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, Sweden.</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, 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Provero, Paolo" sort="Provero, Paolo" uniqKey="Provero P" first="Paolo" last="Provero">Paolo Provero</name><affiliation><nlm:affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10126, Italy.</nlm:affiliation></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><nlm:affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Joo, Jihoon" sort="Joo, Jihoon" uniqKey="Joo J" first="Jihoon" last="Joo">Jihoon Joo</name><affiliation><nlm:affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation></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><nlm:affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kazmi, Nabila" sort="Kazmi, Nabila" uniqKey="Kazmi N" first="Nabila" last="Kazmi">Nabila Kazmi</name><affiliation><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of 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, Norway.</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 Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</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, 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 Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Barrdahl, Myrto" sort="Barrdahl, Myrto" uniqKey="Barrdahl M" first="Myrto" last="Barrdahl">Myrto Barrdahl</name><affiliation><nlm:affiliation>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg, Germany.</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, Norway.</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, Department of Pathology, The University of Melbourne, 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>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</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>International Agency for Research on Cancer, Lyon, France.</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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</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 & Community Medicine, University of Bristol, BS8 2BN, UK.</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>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:27632354</idno><idno type="pmid">27632354</idno><idno type="doi">10.1002/ijc.30431</idno><idno type="wicri:Area/PubMed/Corpus">001377</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001377</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk.</title><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name><affiliation><nlm:affiliation>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, 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>Department of Evolutionary Biology and Environmental Studies, University of Zurich, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Haycock, Philip" sort="Haycock, Philip" uniqKey="Haycock P" first="Philip" last="Haycock">Philip Haycock</name><affiliation><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN, 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>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</nlm:affiliation></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><nlm:affiliation>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</nlm:affiliation></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><nlm:affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Chung, Jessica" sort="Chung, Jessica" uniqKey="Chung J" first="Jessica" last="Chung">Jessica Chung</name><affiliation><nlm:affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Fasanelli, Francesca" sort="Fasanelli, Francesca" uniqKey="Fasanelli F" first="Francesca" last="Fasanelli">Francesca Fasanelli</name><affiliation><nlm:affiliation>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="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="Grankvist, Kjell" sort="Grankvist, Kjell" uniqKey="Grankvist K" first="Kjell" last="Grankvist">Kjell Grankvist</name><affiliation><nlm:affiliation>Department of Biobank Research, Umeå University, 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, Sweden.</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, 10126, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Provero, Paolo" sort="Provero, Paolo" uniqKey="Provero P" first="Paolo" last="Provero">Paolo Provero</name><affiliation><nlm:affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10126, Italy.</nlm:affiliation></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><nlm:affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Joo, Jihoon" sort="Joo, Jihoon" uniqKey="Joo J" first="Jihoon" last="Joo">Jihoon Joo</name><affiliation><nlm:affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</nlm:affiliation></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><nlm:affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kazmi, Nabila" sort="Kazmi, Nabila" uniqKey="Kazmi N" first="Nabila" last="Kazmi">Nabila Kazmi</name><affiliation><nlm:affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of 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, Norway.</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 Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</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, 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 Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Barrdahl, Myrto" sort="Barrdahl, Myrto" uniqKey="Barrdahl M" first="Myrto" last="Barrdahl">Myrto Barrdahl</name><affiliation><nlm:affiliation>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg, Germany.</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, Norway.</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, Department of Pathology, The University of Melbourne, 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>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</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>International Agency for Research on Cancer, Lyon, France.</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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</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>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</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 & Community Medicine, University of Bristol, BS8 2BN, UK.</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>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.</nlm:affiliation></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="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="genetics" xml:lang="en"><term>Lung Neoplasms</term><term>Smoking</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Microarray Analysis</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></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27632354</PMID><DateCreated><Year>2016</Year><Month>09</Month><Day>15</Day></DateCreated><DateCompleted><Year>2017</Year><Month>05</Month><Day>08</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1097-0215</ISSN><JournalIssue CitedMedium="Internet"><Volume>140</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Jan</Month><Day>01</Day></PubDate></JournalIssue><Title>International journal of cancer</Title><ISOAbbreviation>Int. J. Cancer</ISOAbbreviation></Journal><ArticleTitle>DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk.</ArticleTitle><Pagination><MedlinePgn>50-61</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/ijc.30431</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>© 2016 UICC.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Baglietto</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy, Villejuif, F-94805, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ponzi</LastName><ForeName>Erica</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Evolutionary Biology and Environmental Studies, University of Zurich, Switzerland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haycock</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, BS8 2BN, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hodge</LastName><ForeName>Allison</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bianca Assumma</LastName><ForeName>Manuela</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jung</LastName><ForeName>Chol-Hee</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chung</LastName><ForeName>Jessica</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Victorian Life Sciences Computation Initiative, The University of Melbourne, Victoria, 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fasanelli</LastName><ForeName>Francesca</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>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 and Center for Cancer Prevention (CPO), 10126, Torino.</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><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>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>Grankvist</LastName><ForeName>Kjell</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Biobank Research, Umeå University, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansson</LastName><ForeName>Mikael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Radiation Sciences, Umeå University, Sweden.</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, 10126, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Provero</LastName><ForeName>Paolo</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Molecular Biotechnology and Health Sciences, Università di Torino, 10126, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Ee Ming</ForeName><Initials>EM</Initials><AffiliationInfo><Affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Joo</LastName><ForeName>Jihoon</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>English</LastName><ForeName>Dallas R</ForeName><Initials>DR</Initials><AffiliationInfo><Affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kazmi</LastName><ForeName>Nabila</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of 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, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Faltus</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ - German Cancer Research Center, Heidelberg, 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, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Risch</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Cancer Research and Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Epigenomics and Cancer Risk Factors, DKFZ - German Cancer Research Center, Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barrdahl</LastName><ForeName>Myrto</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Cancer Epidemiology, DKFZ - German Cancer Research Center, Heidelberg, Germany.</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, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Southey</LastName><ForeName>Melissa C</ForeName><Initials>MC</Initials><AffiliationInfo><Affiliation>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giles</LastName><ForeName>Graham G</ForeName><Initials>GG</Initials><AffiliationInfo><Affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansson</LastName><ForeName>Mattias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>International Agency for Research on Cancer, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vineis</LastName><ForeName>Paolo</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>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><Author ValidYN="Y"><LastName>Polidoro</LastName><ForeName>Silvia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</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 & Community Medicine, University of Bristol, BS8 2BN, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Severi</LastName><ForeName>Gianluca</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy, Villejuif, F-94805, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>HuGeF, Human Genetics Foundation, Torino, 10126, Italy.</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></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>10</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Int J Cancer</MedlineTA><NlmUniqueID>0042124</NlmUniqueID><ISSNLinking>0020-7136</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>9007-49-2</RegistryNumber><NameOfSubstance UI="D004247">DNA</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D016022" MajorTopicYN="N">Case-Control Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004247" MajorTopicYN="N">DNA</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019175" MajorTopicYN="Y">DNA Methylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055088" MajorTopicYN="N">Early Detection of Cancer</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D044127" MajorTopicYN="N">Epigenesis, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D046228" MajorTopicYN="N">Microarray Analysis</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012907" MajorTopicYN="N">Smoking</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">DNA methylation</Keyword><Keyword MajorTopicYN="Y">lung cancer risk</Keyword><Keyword MajorTopicYN="Y">smoking</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>03</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>07</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>9</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>5</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>9</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27632354</ArticleId><ArticleId IdType="doi">10.1002/ijc.30431</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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