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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | International Journal of Cancer |
| Vol/bind | 148 |
| Udgave nummer | 5 |
| Sider (fra-til) | 1077-1086 |
| ISSN | 0020-7136 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Publisher Copyright:© 2020 UICC
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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.; 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.
I: International Journal of Cancer, Bind 148, Nr. 5, 2021, s. 1077-1086.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
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 - Funding Information: Dr. Amos is a research scholar of the Cancer Prevention Research Institute of Texas (CPRIT). His research is partially funded by CPRIT grant RR170048 and by NIH/NCI grant U19CA203654. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. The Boston Lung Cancer Study was funded by NIH (NCI) U01CA209414 (PI: Christiani). The EAGLE study was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS. The Multiethnic Cohort Study is supported by the National Institutes of Health (CA164973). The CARET study was supported by the National Institutes of Health/National Cancer Institute: UM1 CA167462 (PI: Goodman), U01CA6367307 (PIs: Omen, Goodman), R01 CA111703 (PI: Chen) and U01 CA167462 (PI: Chen). Philip C Haycock is supported by Cancer Research UK (C18281/A19169). Wen Zhou was supported by China Scholarship Council and Nanjing Medical University. Funding Information: Dr. Amos is a research scholar of the Cancer Prevention Research Institute of Texas (CPRIT). His research is partially funded by CPRIT grant RR170048 and by NIH/NCI grant U19CA203654. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. The Boston Lung Cancer Study was funded by NIH (NCI) U01CA209414 (PI: Christiani). The EAGLE study was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS. The Multiethnic Cohort Study is supported by the National Institutes of Health (CA164973). The CARET study was supported by the National Institutes of Health/National Cancer Institute: UM1 CA167462 (PI: Goodman), U01CA6367307 (PIs: Omen, Goodman), R01 CA111703 (PI: Chen) and U01 CA167462 (PI: Chen). Philip C Haycock is supported by Cancer Research UK (C18281/A19169). Wen Zhou was supported by China Scholarship Council and Nanjing Medical University. Funding Information: Cancer Prevention and Research Institute of Texas, Grant/Award Number: RR170048; Cancer Research UK, Grant/Award Numbers: C18281, A19169; Foundation for the National Institutes of Health, Grant/Award Numbers: CA164973, R01 CA111703, U01 CA167462, U01 CA209414, U01 CA6367307, U19 CA203654, UM1 CA167462 Funding information F TS Publisher Copyright: © 2020 UICC
PY - 2021
Y1 - 2021
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 - body mass index
KW - causal relationship
KW - lung cancer
KW - Mendelian randomization
KW - smoking phenotypes
U2 - 10.1002/ijc.33292
DO - 10.1002/ijc.33292
M3 - Journal article
C2 - 32914876
AN - SCOPUS:85091367419
VL - 148
SP - 1077
EP - 1086
JO - Acta - Unio Internationalis Contra Cancrum
JF - Acta - Unio Internationalis Contra Cancrum
SN - 0898-6924
IS - 5
ER -