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Olle Melander

Principal investigator

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Causal relationships between body mass index, smoking and lung cancer : Univariable and multivariable Mendelian randomization

Author

  • Wen Zhou
  • Geoffrey Liu
  • Rayjean J. Hung
  • Philip C. Haycock
  • Melinda C. Aldrich
  • Angeline S. Andrew
  • Susanne M. Arnold
  • Heike Bickeböller
  • Stig E Bojesen
  • Paul Brennan
  • Hans Brunnström
  • Olle Melander
  • Neil E. Caporaso
  • Maria Teresa Landi
  • Chu Chen
  • Gary E. Goodman
  • David C. Christiani
  • Angela Cox
  • John K. Field
  • Mikael Johansson
  • Lambertus A. Kiemeney
  • Stephen Lam
  • Philip Lazarus
  • Loïc Le Marchand
  • Gad Rennert
  • Angela Risch
  • Matthew B. Schabath
  • Sanjay S. Shete
  • Adonina Tardón
  • Shanbeh Zienolddiny
  • Hongbing Shen
  • Christopher I. Amos

Summary, in English

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.

Department/s

  • LUCC - Lund University Cancer Centre
  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs
  • Tumor microenvironment
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension

Publishing year

2021

Language

English

Pages

1077-1086

Publication/Series

International Journal of Cancer

Volume

148

Issue

5

Document type

Journal article

Publisher

John Wiley and Sons

Topic

  • Cancer and Oncology

Keywords

  • body mass index
  • causal relationship
  • lung cancer
  • Mendelian randomization
  • smoking phenotypes

Status

Published

Research group

  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 0020-7136