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

Zhou, Wen, Liu, Geoffrey, Hung, Rayjean J et al. (2021). Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization. . 148(5), 1077-1086. 10.1002/ijc.33292

cited authors

  • 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

fiu authors

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.

publication date

  • March 1, 2021

keywords

  • Body Mass Index
  • Genome-Wide Association Study
  • Humans
  • Lung Neoplasms
  • Mendelian Randomization Analysis
  • Obesity
  • Polymorphism, Single Nucleotide
  • Smoking

Digital Object Identifier (DOI)

Medium

  • Print-Electronic

start page

  • 1077

end page

  • 1086

volume

  • 148

issue

  • 5