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dc.contributor.authorLi, Yafang
dc.contributor.authorXiao, Xiangjun
dc.contributor.authorHan, Younghun
dc.contributor.authorGorlova, Olga
dc.contributor.authorQian, David
dc.contributor.authorLeighl, Natasha
dc.contributor.authorJohansen, Jakob S
dc.contributor.authorBarnett, Matt
dc.contributor.authorChen, Chu
dc.contributor.authorGoodman, Gary
dc.contributor.authorCox, Angela
dc.contributor.authorTaylor, Fiona
dc.contributor.authorWoll, Penella
dc.contributor.authorWichmann, H -Erich
dc.contributor.authorManz, Judith
dc.contributor.authorMuley, Thomas
dc.contributor.authorRisch, Angela
dc.contributor.authorRosenberger, Albert
dc.contributor.authorArnold, Susanne M
dc.contributor.authorHaura, Eric B
dc.contributor.authorBolca, Ciprian
dc.contributor.authorHolcatova, Ivana
dc.contributor.authorJanout, Vladimir
dc.contributor.authorKontic, Milica
dc.contributor.authorLissowska, Jolanta
dc.contributor.authorMukeria, Anush
dc.contributor.authorOgnjanovic, Simona
dc.contributor.authorOrlowski, Tadeusz M
dc.contributor.authorScelo, Ghislaine
dc.contributor.authorSwiatkowska, Beata
dc.contributor.authorZaridze, David
dc.contributor.authorBakke, Per
dc.contributor.authorSkaug, Vidar
dc.contributor.authorZienolddiny, Shanbeh
dc.contributor.authorDuell, Eric J
dc.contributor.authorButler, Lesley M
dc.contributor.authorHoulston, Richard
dc.contributor.authorSoler Artigas, María
dc.contributor.authorGrankvist, Kjell
dc.contributor.authorJohansson, Mikael
dc.contributor.authorShepherd, Frances A
dc.contributor.authorMarcus, Michael W
dc.contributor.authorBrunnström, Hans
dc.contributor.authorManjer, Jonas
dc.contributor.authorMelander, Olle
dc.contributor.authorMuller, David C
dc.contributor.authorOvervad, Kim
dc.contributor.authorTrichopoulou, Antonia
dc.contributor.authorTumino, Rosario
dc.contributor.authorLiu, Geoffrey
dc.contributor.authorBojesen, Stig E
dc.contributor.authorWu, Xifeng
dc.contributor.authorMarchand, Loic Le
dc.contributor.authorAlbanes, Demetrios
dc.contributor.authorBickeböller, Heike
dc.contributor.authorAldrich, Melinda C
dc.contributor.authorBush, William S
dc.contributor.authorTardon, Adonina
dc.contributor.authorRennert, Gad
dc.contributor.authorTeare, M Dawn
dc.contributor.authorField, John K
dc.contributor.authorKiemeney, Lambertus A
dc.contributor.authorLazarus, Philip
dc.contributor.authorHaugen, Aage
dc.contributor.authorLam, Stephen
dc.contributor.authorSchabath, Matthew B
dc.contributor.authorAndrew, Angeline S
dc.contributor.authorBertazzi, Pier Alberto
dc.contributor.authorPesatori, Angela C
dc.contributor.authorChristiani, David C
dc.contributor.authorCaporaso, Neil
dc.contributor.authorJohansson, Mattias
dc.contributor.authorMcKay, James D
dc.contributor.authorBrennan, Paul
dc.contributor.authorHung, Rayjean J
dc.contributor.authorAmos, Christopher I
dc.date.accessioned2018-12-04T09:23:29Z
dc.date.available2018-12-04T09:23:29Z
dc.date.issued2018-03
dc.identifier.citationCarcinogenesis 2018, 39 (3):336en
dc.identifier.issn0143-3334
dc.identifier.issn1460-2180
dc.identifier.doi10.1093/carcin/bgx113
dc.identifier.urihttp://hdl.handle.net/10146/618229
dc.description.abstractNon-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
dc.language.isoenen
dc.relation.urlhttps://academic.oup.com/carcin/article/39/3/336/4558711en
dc.rightsArchived with thanks to Carcinogenesisen
dc.subjectsmokingen
dc.subjectlung canceren
dc.subjectcarcinogenesisen
dc.titleGenome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian populationen
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicineen
dc.identifier.journalCarcinogenesisen
dc.contributor.institutionBiomedical Data Science Department, Dartmouth College, Hanover, NH, USA
dc.contributor.institutionBiomedical Data Science Department, Dartmouth College, Hanover, NH, USA
dc.contributor.institutionBiomedical Data Science Department, Dartmouth College, Hanover, NH, USA
dc.contributor.institutionBiomedical Data Science Department, Dartmouth College, Hanover, NH, USA
dc.contributor.institutionBiomedical Data Science Department, Dartmouth College, Hanover, NH, USA
dc.contributor.institutionDepartment of Medicine, The Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
dc.contributor.institutionDepartment of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen University, Herlev, Denmark
dc.contributor.institutionPublic Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
dc.contributor.institutionPublic Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
dc.contributor.institutionPublic Health Sciences Division, Cancer Prevention Program, Swedish Medical Center, Seattle, WA, USA
dc.contributor.institutionDepartment of Oncology, University of Sheffield, Sheffield UK
dc.contributor.institutionDepartment of Oncology, University of Sheffield, Sheffield UK
dc.contributor.institutionDepartment of Oncology, University of Sheffield, Sheffield UK
dc.contributor.institutionInstitute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany
dc.contributor.institutionInstitute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany
dc.contributor.institutionBiobank and Tumor Documentation, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany
dc.contributor.institutionBiobank and Tumor Documentation, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany
dc.contributor.institutionDepartment of Genetic Epidemiology, Medical School, Georg-August University of Göttingen, Göttingen, Germany
dc.contributor.institutionMarkey Cancer Center, University of Kentucky, Lexington, KY, USA
dc.contributor.institutionDepartment of Thoracic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
dc.contributor.institutionThoracic Surgery Division, “Marius Nasta” National Institute of Pneumology, București, Romania
dc.contributor.institutionFaculty of Medicine, University of Ostrava, Ostrava, Czech Republic
dc.contributor.institutionFaculty of Medicine, University of Ostrava, Ostrava, Czech Republic
dc.contributor.institutionInternal Medicine, School of Medicine, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia
dc.contributor.institutionDepartment of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center, Institute of Oncology, Warsaw, Pol
dc.contributor.institutionDepartment of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Centre, Moscow, Russia
dc.contributor.institutionInternational Organization for Cancer Prevention and Research, Belgrade, Serbia
dc.contributor.institutionDepartment of Thoracic Surgery, National Institute of Tuberculosis and Lung Diseases, Warsaw, Pol
dc.contributor.institutionInternational Agency for Research on Cancer (IARC), Genetic Epidemiology Group, Lyon, France
dc.contributor.institutionDepartment of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Łódź, Pol
dc.contributor.institutionDepartment of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Centre, Moscow, Russia
dc.contributor.institutionDepartment of Clinical Science, University of Bergen, Bergen, Norway
dc.contributor.institutionDepartment of Toxicology, National Institute of Occupational Health, Oslo, Norway
dc.contributor.institutionDepartment of Toxicology, National Institute of Occupational Health, Oslo, Norway
dc.contributor.institutionUnit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
dc.contributor.institutionUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
dc.contributor.institutionThe Institute of Cancer Research, London, UK
dc.contributor.institutionDepartment of Health Sciences, Genetic Epidemiology Group, University of Leicester, Leicester, UK
dc.contributor.institutionDepartment of Medical Biosciences, Umeå University, Umeå, Sweden
dc.contributor.institutionDepartment of Radiation Sciences, Umeå University, Umeå, Sweden
dc.contributor.institutionMedical Oncology Toronto, Princess Margaret Hospital, Toronto, ON, Canada
dc.contributor.institutionDepartment of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
dc.contributor.institutionDepartment of Clinical Sciences, Lund University, Lund, Sweden
dc.contributor.institutionDepartment of Internal Medicine, Skåne University Hospital, Malmö, Sweden
dc.contributor.institutionDepartment of Clinical Sciences, Lund University, Lund, Sweden
dc.contributor.institutionDepartment of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, London, UK
dc.contributor.institutionSection for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark
dc.contributor.institutionDepartment of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece
dc.contributor.institutionMolecular and Nutritional Epidemiology Unit, CSPO (Cancer Research and Prevention Centre), Scientific Institute of Tuscany, Florence, Italy
dc.contributor.institutionPrincess Margaret Cancer Centre, Toronto, ON M5G, Canada
dc.contributor.institutionDepartment of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
dc.contributor.institutionDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
dc.contributor.institutionEpidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
dc.contributor.institutionDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, MD, USA
dc.contributor.institutionDepartment of Genetic Epidemiology, University Medical Center, Georg-August University Göttingen, Göttingen, Germany
dc.contributor.institutionDepartment of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA
dc.contributor.institutionDepartment of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
dc.contributor.institutionMedicina, IUOPA-Universidad de Oviedo, Oviedo, Spain
dc.contributor.institutionTechnion Faculty of Medicine, Clalit National Cancer Control Center, Carmel Medical Center, Haifa, Israel
dc.contributor.institutionGenetic Epidemiology, School of Health and Related Research, University of Sheffield, Sheffield, UK
dc.contributor.institutionInstitute of Translational Medicine, University of Liverpool, Liverpool, UK
dc.contributor.institutionDepartment for Health Evidence, Radboud University Medical Center, Nijmegen EZ, Netherlands
dc.contributor.institutionDepartment of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, USA
dc.contributor.institutionDepartment of Toxicology, National Institute of Occupational Health, Oslo, Norway
dc.contributor.institutionDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada
dc.contributor.institutionDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
dc.contributor.institutionDepartment of Epidemiology, Norris Cotton Cancer Center, Dartmouth College, Hanover, NH, USA
dc.contributor.institutionDepartment of Preventive Medicine, IRCCS Foundation Cà Granda Ospedale, Maggiore Policlinico, University of Milan, Milan, Italy
dc.contributor.institutionDepartment of Clinical Sciences and Community Health–DISCCO, University of Milan, Milan, Italy
dc.contributor.institutionDepartment of Epidemiology, Harvard School of Public Health, Boston, MA, USA
dc.contributor.institutionDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, MD, USA
dc.contributor.institutionInternational Agency for Research on Cancer, World Health Organization, Lyon, France
dc.contributor.institutionInternational Agency for Research on Cancer (IARC), Genetic Epidemiology Group, Lyon, France
dc.contributor.institutionInternational Agency for Research on Cancer, World Health Organization, Lyon, France
dc.contributor.institutionDivision of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
dc.contributor.institutionBiomedical Data Science Department, Dartmouth College, Hanover, NH, USA
html.description.abstractNon-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.


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