Zhou, W., Liu, G., Hung, R.J. et al. (29 more authors) (2021) Causal relationships between body mass index, smoking, and lung cancer: univariable and multivariable mendelian randomization. International Journal of Cancer, 148 (5). pp. 1077-1086. ISSN 0020-7136
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 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, PMVMR = 0.011), and an inverse effect on lung adenocarcinoma (ORMVMR = 0.86, 95% CI = 0.77‐0.96, PMVMR = 0.008) 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 = 0.036), but this effect disappeared after adjustment of smoking (ORMVMR = 1.02, 95% CI = 0.90‐1.16, PMVMR = 0.746). 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.
Metadata
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Copyright, Publisher and Additional Information: | © 2020 UICC. This is an author-produced version of a paper subsequently published in International Journal of Cancer. Uploaded in accordance with the publisher's self-archiving policy. | ||||||||
Keywords: | Causal relationship; Mendelian randomization; body mass index; lung cancer; smoking phenotypes | ||||||||
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Institution: | The University of Sheffield | ||||||||
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Oncology (Sheffield) |
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Depositing User: | Symplectic Sheffield | ||||||||
Date Deposited: | 14 Sep 2020 11:24 | ||||||||
Last Modified: | 27 Jan 2022 11:21 | ||||||||
Status: | Published | ||||||||
Publisher: | Wiley | ||||||||
Refereed: | Yes | ||||||||
Identification Number: | https://doi.org/10.1002/ijc.33292 | ||||||||
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