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

Zhou, Wen ; Liu, Geoffrey ; Hung, Rayjean J. ; Haycock, Philip C. ; Aldrich, Melinda C. ; Andrew, Angeline S. ; Arnold, Susanne M. ; Bickeböller, Heike ; Bojesen, Stig E and Brennan, Paul , et al. (2020) In International Journal of Cancer
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
body mass index, causal relationship, lung cancer, Mendelian randomization, smoking phenotypes
in
International Journal of Cancer
publisher
John Wiley and Sons
external identifiers
  • scopus:85091367419
  • pmid:32914876
ISSN
0020-7136
DOI
10.1002/ijc.33292
language
English
LU publication?
yes
id
6c024f3d-4b48-4c74-8886-7a570b828622
date added to LUP
2020-11-02 16:04:00
date last changed
2021-01-06 04:37:23
@article{6c024f3d-4b48-4c74-8886-7a570b828622,
  abstract     = {<p>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<sup>−4</sup>). After adjustment of smoking behaviors using multivariable Mendelian randomization (MVMR), a direct causal effect on small cell lung cancer (OR<sub>MVMR</sub> = 1.28, 95% CI = 1.06-1.55, P<sub>MVMR</sub> =.011), and an inverse effect on lung adenocarcinoma (OR<sub>MVMR</sub> = 0.86, 95% CI = 0.77-0.96, P<sub>MVMR</sub> =.008) were observed. A weak increased risk of lung squamous cell carcinoma was observed for higher BMI in univariable Mendelian randomization (UVMR) analysis (OR<sub>UVMR</sub> = 1.19, 95% CI = 1.01-1.40, P<sub>UVMR</sub> =.036), but this effect disappeared after adjustment of smoking (OR<sub>MVMR</sub> = 1.02, 95% CI = 0.90-1.16, P<sub>MVMR</sub> =.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.</p>},
  author       = {Zhou, Wen and Liu, Geoffrey and Hung, Rayjean J. and Haycock, Philip C. and Aldrich, Melinda C. and Andrew, Angeline S. and Arnold, Susanne M. and Bickeböller, Heike and Bojesen, Stig E and Brennan, Paul and Brunnström, Hans and Melander, Olle and Caporaso, Neil E. and Landi, Maria Teresa and Chen, Chu and Goodman, Gary E. and Christiani, David C. and Cox, Angela and Field, John K. and Johansson, Mikael and Kiemeney, Lambertus A. and Lam, Stephen and Lazarus, Philip and Le Marchand, Loïc and Rennert, Gad and Risch, Angela and Schabath, Matthew B. and Shete, Sanjay S. and Tardón, Adonina and Zienolddiny, Shanbeh and Shen, Hongbing and Amos, Christopher I.},
  issn         = {0020-7136},
  language     = {eng},
  month        = {09},
  publisher    = {John Wiley and Sons},
  series       = {International Journal of Cancer},
  title        = {Causal relationships between body mass index, smoking and lung cancer : Univariable and multivariable Mendelian randomization},
  url          = {http://dx.doi.org/10.1002/ijc.33292},
  doi          = {10.1002/ijc.33292},
  year         = {2020},
}