TY - JOUR
T1 - Causal relationships between body mass index, smoking and lung cancer
T2 - Univariable and multivariable Mendelian randomization
AU - Zhou, Wen
AU - Liu, Geoffrey
AU - Hung, Rayjean J.
AU - Haycock, Philip C.
AU - Aldrich, Melinda C.
AU - Andrew, Angeline S.
AU - Arnold, Susanne M.
AU - Bickeböller, Heike
AU - Bojesen, Stig E.
AU - Brennan, Paul
AU - Brunnström, Hans
AU - Melander, Olle
AU - Caporaso, Neil E.
AU - Landi, Maria Teresa
AU - Chen, Chu
AU - Goodman, Gary E.
AU - Christiani, David C.
AU - Cox, Angela
AU - Field, John K.
AU - Johansson, Mikael
AU - Kiemeney, Lambertus A.
AU - Lam, Stephen
AU - Lazarus, Philip
AU - Le Marchand, Loïc
AU - Rennert, Gad
AU - Risch, Angela
AU - Schabath, Matthew B.
AU - Shete, Sanjay S.
AU - Tardón, Adonina
AU - Zienolddiny, Shanbeh
AU - Shen, Hongbing
AU - Amos, Christopher I.
N1 - Publisher Copyright:
© 2020 UICC
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
KW - Mendelian randomization
KW - body mass index
KW - causal relationship
KW - lung cancer
KW - smoking phenotypes
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U2 - 10.1002/ijc.33292
DO - 10.1002/ijc.33292
M3 - Article
C2 - 32914876
AN - SCOPUS:85091367419
SN - 0020-7136
VL - 148
SP - 1077
EP - 1086
JO - International journal of cancer
JF - International journal of cancer
IS - 5
ER -