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

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Zhou, Wen, Liu, Geoffrey, Hung, Rayjean J, Haycock, Philip C, Aldrich, Melinda C, Andrew, Angeline S, Arnold, Susanne M, Bickeboeller, Heike, Bojesen, Stig E, Brennan, Paul et al (show 22 more authors) , Brunnstrom, Hans, Melander, Olle, Caporaso, Neil E, Landi, Maria Teresa, Chen, Chu, Goodman, Gary E, Christiani, David C, Cox, Angela, Field, John K ORCID: 0000-0003-3951-6365, Johansson, Mikael, Kiemeney, Lambertus A, Lam, Stephen, Lazarus, Philip, Le Marchand, Loic, Rennert, Gad, Risch, Angela, Schabath, Matthew B, Shete, Sanjay S, Tardon, Adonina, Zienolddiny, Shanbeh, Shen, Hongbing and Amos, Christopher I (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.

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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 (OR_MVMR = 1.28, 95% CI = 1.06-1.55, P_MVMR = .011), and an inverse effect on lung adenocarcinoma (OR_MVMR = 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 (OR_UVMR = 1.19, 95% CI = 1.01-1.40, P_UVMR = .036), but this effect disappeared after adjustment of smoking (OR_MVMR = 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.

Item Type:	Article
Uncontrolled Keywords:	body mass index, causal relationship, lung cancer, Mendelian randomization, smoking phenotypes
Depositing User:	Symplectic Admin
Date Deposited:	14 Sep 2020 12:55
Last Modified:	18 Jan 2023 23:33
DOI:	10.1002/ijc.33292
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3101146