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Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility.
Kachuri, Linda; Johansson, Mattias; Rashkin, Sara R; Graff, Rebecca E; Bossé, Yohan; Manem, Venkata; Caporaso, Neil E; Landi, Maria Teresa; Christiani, David C; Vineis, Paolo; Liu, Geoffrey; Scelo, Ghislaine; Zaridze, David; Shete, Sanjay S; Albanes, Demetrius; Aldrich, Melinda C; Tardón, Adonina; Rennert, Gad; Chen, Chu; Goodman, Gary E; Doherty, Jennifer A; Bickeböller, Heike; Field, John K; Davies, Michael P; Dawn Teare, M; Kiemeney, Lambertus A; Bojesen, Stig E; Haugen, Aage; Zienolddiny, Shanbeh; Lam, Stephen; Le Marchand, Loïc; Cheng, Iona; Schabath, Matthew B; Duell, Eric J; Andrew, Angeline S; Manjer, Jonas; Lazarus, Philip; Arnold, Susanne; McKay, James D; Emami, Nima C; Warkentin, Matthew T; Brhane, Yonathan; Obeidat, Ma'en; Martin, Richard M; Relton, Caroline; Davey Smith, George; Haycock, Philip C; Amos, Christopher I; Brennan, Paul; Witte, John S.
Afiliação
  • Kachuri L; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • Johansson M; Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Rashkin SR; International Agency for Research on Cancer, Lyon, France.
  • Graff RE; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • Bossé Y; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • Manem V; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada.
  • Caporaso NE; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada.
  • Landi MT; Division of Cancer Epidemiology & Genetics, US NCI, Bethesda, MD, USA.
  • Christiani DC; Division of Cancer Epidemiology & Genetics, US NCI, Bethesda, MD, USA.
  • Vineis P; Departments of Environmental Health and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
  • Liu G; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Scelo G; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada.
  • Zaridze D; International Agency for Research on Cancer, Lyon, France.
  • Shete SS; Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.
  • Albanes D; Department of Biostatistics, Division of Basic Sciences, MD Anderson Cancer Center, Houston, TX, USA.
  • Aldrich MC; Division of Cancer Epidemiology & Genetics, US NCI, Bethesda, MD, USA.
  • Tardón A; Department of Thoracic Surgery and Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Rennert G; Faculty of Medicine, University of Oviedo and ISPA and CIBERESP, Campus del Cristo, Oviedo, Spain.
  • Chen C; Clalit National Cancer Control Center, Technion Faculty of Medicine, Haifa, Israel.
  • Goodman GE; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Doherty JA; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Bickeböller H; Department of Population Health Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Field JK; Department of Genetic Epidemiology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany.
  • Davies MP; Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, London, UK.
  • Dawn Teare M; Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, London, UK.
  • Kiemeney LA; Biostatistics Research Group, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
  • Bojesen SE; Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
  • Haugen A; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Zienolddiny S; The National Institute of Occupational Health, Oslo, Norway.
  • Lam S; The National Institute of Occupational Health, Oslo, Norway.
  • Le Marchand L; BC Cancer Agency, Vancouver, BC, Canada.
  • Cheng I; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Schabath MB; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • Duell EJ; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
  • Andrew AS; Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
  • Manjer J; Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
  • Lazarus P; Skåne University Hospital, Lund University, Lund, Sweden.
  • Arnold S; Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
  • McKay JD; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
  • Emami NC; International Agency for Research on Cancer, Lyon, France.
  • Warkentin MT; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • Brhane Y; Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Obeidat M; Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
  • Martin RM; Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Relton C; University of British Columbia, Centre for Heart Lung Innovation, Vancouver, BC, Canada.
  • Davey Smith G; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Haycock PC; Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
  • Amos CI; National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.
  • Brennan P; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Witte JS; Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
Nat Commun ; 11(1): 27, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911640
ABSTRACT
Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1 rg = 0.098, p = 2.3 × 10-8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC rg = 0.137, p = 2.0 × 10-12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals 1.21-1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01-1.35) and lung cancer in never smokers (OR = 1.56, 1.05-2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Pulmão / Neoplasias Pulmonares Tipo de estudo: Estudo observacional / Fatores de risco Limite: Adulto / Idoso / Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Nat Commun Assunto da revista: Biologia / Ciência Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Estados Unidos

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Pulmão / Neoplasias Pulmonares Tipo de estudo: Estudo observacional / Fatores de risco Limite: Adulto / Idoso / Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Nat Commun Assunto da revista: Biologia / Ciência Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Estados Unidos