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Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization.
Zhou, Wen; Liu, Geoffrey; Hung, Rayjean J; Haycock, Philip C; Aldrich, Melinda C; Andrew, Angeline S; Arnold, Susanne M; Bickeböller, Heike; Bojesen, Stig E; Brennan, Paul; Brunnström, Hans; Melander, Olle; Caporaso, Neil E; Landi, Maria Teresa; Chen, Chu; Goodman, Gary E; Christiani, David C; Cox, Angela; Field, John K; Johansson, Mikael; Kiemeney, Lambertus A; Lam, Stephen; Lazarus, Philip; Le Marchand, Loïc; Rennert, Gad; Risch, Angela; Schabath, Matthew B; Shete, Sanjay S; Tardón, Adonina; Zienolddiny, Shanbeh; Shen, Hongbing; Amos, Christopher I.
Afiliação
  • Zhou W; Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
  • Liu G; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA.
  • Hung RJ; Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Haycock PC; Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
  • Aldrich MC; Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
  • Andrew AS; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Arnold SM; Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
  • Bickeböller H; Department of Thoracic Surgery and Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Bojesen SE; Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA.
  • Brennan P; Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA.
  • Brunnström H; Department of Genetic Epidemiology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany.
  • Melander O; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Caporaso NE; Genetic Epidemology Group, International Agency for Research on Cancer, Lyon, France.
  • Landi MT; Clinical Sciences, Lund University, Lund, Sweden.
  • Chen C; Clinical Sciences, Lund University, Lund, Sweden.
  • Goodman GE; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
  • Christiani DC; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
  • Cox A; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center and Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
  • Field JK; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center and Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
  • Johansson M; Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Kiemeney LA; Academic Unit of Clinical Oncology, University of Sheffield, Sheffield, UK.
  • Lam S; Department of Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, The University of Liverpool Cancer Research Centre, Liverpool, UK.
  • Lazarus P; Department of Radiation Sciences, Umeå University, Umea, Sweden.
  • Le Marchand L; Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Rennert G; Department of Integrative Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
  • Risch A; Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA.
  • Schabath MB; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
  • Shete SS; Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
  • Tardón A; Department of Biosciences, Allergy-Cancer-BioNano Research Centre, University of Salzburg, Salzburg, Austria.
  • Zienolddiny S; Cancer Cluster Salzburg, University of Salzburg, Salzburg, Austria.
  • Shen H; Division of Cancer Epigenomics, DKFZ - German Cancer Research Center, Heidelberg, Germany.
  • Amos CI; Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Int J Cancer ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914876
ABSTRACT
At the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two-sample univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological subtypes based on an aggregated genome-wide association studies (GWASs) analysis of lung cancer in 29 266 cases and 56 450 controls. We observed a positive causal effect for high BMI on occurrence of small-cell lung cancer (odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.24-2.06, P = 2.70 × 10-4 ). After adjustment of smoking behaviors using multivariable Mendelian randomization (MVMR), a direct causal effect on small cell lung cancer (ORMVMR = 1.28, 95% CI = 1.06-1.55, PMVMR = .011), and an inverse effect on lung adenocarcinoma (ORMVMR = 0.86, 95% CI = 0.77-0.96, PMVMR = .008) were observed. A weak increased risk of lung squamous cell carcinoma was observed for higher BMI in univariable Mendelian randomization (UVMR) analysis (ORUVMR = 1.19, 95% CI = 1.01-1.40, PUVMR = .036), but this effect disappeared after adjustment of smoking (ORMVMR = 1.02, 95% CI = 0.90-1.16, PMVMR = .746). These results highlight the histology-specific impact of BMI on lung carcinogenesis and imply mediator role of smoking behaviors in the association between BMI and lung cancer.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo observacional / Estudo prognóstico Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo observacional / Estudo prognóstico Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China
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