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

Zhou, Wen (author)
Nanjing Medical University,Baylor College of Medicine
Liu, Geoffre (author)
Princess Margaret Hospital University of Toronto
Hung, Rayjean J. (author)
University of Toronto,Sinai Health System
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Haycock, Philip C. (author)
University of Bristol,University of Washington
Aldrich, Melinda C. (author)
Vanderbilt University
Andrew, Angeline S. (author)
Dartmouth College
Arnold, Susanne M. (author)
University of Kentucky Medical Center
Bickeboeller, Heike (author)
University Medical Center Göttingen
Bojesen, Stig E. (author)
Copenhagen University Hospital
Brennan, Paul (author)
International Agency for Research on Cancer, World Health Organization
Brunnström, Hans (author)
Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Melander, Olle (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Caporaso, Neil E. (author)
National Cancer Institute, NCI
Landi, Maria Teresa (author)
National Cancer Institute, NCI
Chen, Chu (author)
Harvard T.H. Chan School of Public Health
Goodman, Gary E. (author)
University of Washington
Christiani, David C. (author)
Cox, Angela (author)
University of Sheffield
Field, John K. (author)
University of Liverpool
Johansson, Mikael (author)
Umeå University,Umeå universitet,Onkologi
Kiemeney, Lambertus A. (author)
Radboud University Medical Center
Lam, Stephen (author)
British Columbia Cancer Agency
Lazarus, Philip (author)
Washington State University
Le Marchand, Loic (author)
University of Hawaii Cancer Center
Rennert, Gad (author)
Technion - Israel Institute of Technology
Risch, Angela (author)
University Hospital Heidelberg,German Center for Lung Research (DZL),University of Salzburg,German Cancer Research Centre
Schabath, Matthew B. (author)
H. Lee Moffitt Cancer Center & Research Institute
Shete, Sanjay S. (author)
University of Texas MD Anderson Cancer Center
Tardon, Adonina (author)
University of Oviedo
Zienolddiny, Shanbeh (author)
National Institute of Occupational Health, Norway
Shen, Hongbing (author)
Nanjing Medical University
Amos, Christopher I. (author)
Baylor College of Medicine
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 (creator_code:org_t)
2020-09-23
2021
English.
In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 148:5, s. 1077-1086
Related links:
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http://dx.doi.org/10...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 x 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,P-MVMR= .011), and an inverse effect on lung adenocarcinoma (ORMVMR= 0.86, 95% CI = 0.77-0.96,P-MVMR= .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,P-UVMR= .036), but this effect disappeared after adjustment of smoking (ORMVMR= 1.02, 95% CI = 0.90-1.16,P-MVMR= .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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

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

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ref (subject category)
art (subject category)

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