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; 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.

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

Mark

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. (2021) In International Journal of Cancer 148(5). p.1077-1086

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 (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.
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Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/6c024f3d-4b48-4c74-8886-7a570b828622

author

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. (More)

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 ^LU

; Melander, Olle ^LU ; 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 and Amos, Christopher I. (Less)

organization

publishing date

2021

type

Contribution to journal

publication status

published

subject

Cancer and Oncology

keywords

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

in

International Journal of Cancer

volume

148

issue

5

pages

1077 - 1086

publisher

John Wiley & Sons Inc.

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

2023-04-10 22:19:00

@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}},
  keywords     = {{body mass index; causal relationship; lung cancer; Mendelian randomization; smoking phenotypes}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1077--1086}},
  publisher    = {{John Wiley & Sons Inc.}},
  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}},
  volume       = {{148}},
  year         = {{2021}},
}

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