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

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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.

In: International Journal of Cancer, Vol. 148, No. 5, 2021, p. 1077-1086.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zhou, W, Liu, G, Hung, RJ, Haycock, PC, Aldrich, MC, Andrew, AS, Arnold, SM, Bickeböller, H, Bojesen, SE, Brennan, P, Brunnström, H, Melander, O, Caporaso, NE, Landi, MT, Chen, C, Goodman, GE, Christiani, DC, Cox, A, Field, JK, Johansson, M, Kiemeney, LA, Lam, S, Lazarus, P, Le Marchand, L, Rennert, G, Risch, A, Schabath, MB, Shete, SS, Tardón, A, Zienolddiny, S, Shen, H & Amos, CI 2021, 'Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization', International Journal of Cancer, vol. 148, no. 5, pp. 1077-1086. https://doi.org/10.1002/ijc.33292

APA

Zhou, W., Liu, G., Hung, R. J., Haycock, P. C., Aldrich, M. C., Andrew, A. S., Arnold, S. M., Bickeböller, H., Bojesen, S. E., Brennan, P., Brunnström, H., Melander, O., Caporaso, N. E., Landi, M. T., Chen, C., Goodman, G. E., Christiani, D. C., Cox, A., Field, J. K., ... Amos, C. I. (2021). Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization. International Journal of Cancer, 148(5), 1077-1086. https://doi.org/10.1002/ijc.33292

Vancouver

Zhou W, Liu G, Hung RJ, Haycock PC, Aldrich MC, Andrew AS et al. Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization. International Journal of Cancer. 2021;148(5):1077-1086. https://doi.org/10.1002/ijc.33292

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. ; 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. In: International Journal of Cancer. 2021 ; Vol. 148, No. 5. pp. 1077-1086.

Bibtex

@article{f40ed58bed63488690fe8b7cc9af9490,
title = "Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization",
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.",
keywords = "body mass index, causal relationship, lung cancer, Mendelian randomization, smoking phenotypes",
author = "Wen Zhou and Geoffrey Liu and Hung, {Rayjean J.} and Haycock, {Philip C.} and Aldrich, {Melinda C.} and Andrew, {Angeline S.} and Arnold, {Susanne M.} and Heike Bickeb{\"o}ller and Bojesen, {Stig E.} and Paul Brennan and Hans Brunnstr{\"o}m and Olle Melander and Caporaso, {Neil E.} and Landi, {Maria Teresa} and Chu Chen and Goodman, {Gary E.} and Christiani, {David C.} and Angela Cox and Field, {John K.} and Mikael Johansson and Kiemeney, {Lambertus A.} and Stephen Lam and Philip Lazarus and {Le Marchand}, Lo{\"i}c and Gad Rennert and Angela Risch and Schabath, {Matthew B.} and Shete, {Sanjay S.} and Adonina Tard{\'o}n and Shanbeh Zienolddiny and Hongbing Shen and Amos, {Christopher I.}",
note = "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: {\textcopyright} 2020 UICC",
year = "2021",
doi = "10.1002/ijc.33292",
language = "English",
volume = "148",
pages = "1077--1086",
journal = "Acta - Unio Internationalis Contra Cancrum",
issn = "0898-6924",
publisher = "JohnWiley & Sons, Inc.",
number = "5",

}

RIS

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 -

ID: 302169290