Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.

<h4>Background</h4>Lung cancer is the major cause of mortality in tumor patients. While its incidence rate has recently declined, it is still far from satisfactory and its potential modifiable risk factors should be explored.<h4>Methods</h4>We performed a two-sample Mendelian...

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Autores principales:	Jie Ding, Zhenxing Tu, Hongquan Chen, Zhiguang Liu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e98db1558ad140a096c7e382b05a61e6
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spelling	oai:doaj.org-article:e98db1558ad140a096c7e382b05a61e62021-12-02T20:16:49ZIdentifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.1932-620310.1371/journal.pone.0258498https://doaj.org/article/e98db1558ad140a096c7e382b05a61e62021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258498https://doaj.org/toc/1932-6203<h4>Background</h4>Lung cancer is the major cause of mortality in tumor patients. While its incidence rate has recently declined, it is still far from satisfactory and its potential modifiable risk factors should be explored.<h4>Methods</h4>We performed a two-sample Mendelian randomization (MR) study to investigate the causal relationship between potentially modifiable risk factors (namely smoking behavior, alcohol intake, anthropometric traits, blood pressure, lipidemic traits, glycemic traits, and fasting insulin) and lung cancer. Besides, a bi-directional MR analysis was carried out to disentangle the complex relationship between different risk factors. Inverse-variance weighted (IVW) was utilized to combine the estimation for each SNP. Cochrane's Q value was used to evaluate heterogeneity and two methods, including MR-Egger intercept and MR-PRESSO, were adopted to detect horizontal pleiotropy.<h4>Results</h4>Three kinds of smoking behavior were all causally associated with lung cancer. Overall, smokers were more likely to suffer from lung cancer compared with non-smokers (OR = 2.58 [1.95, 3.40], p-value = 2.07 x 10-11), and quitting smoking could reduce the risk (OR = 4.29[2.60, 7.07], p-value = 1.23 x 10-8). Furthermore, we found a dose-response relationship between the number of cigarettes and lung cancer (OR = 6.10 [5.35, 6.96], p-value = 4.43x10-161). Lower HDL cholesterol could marginally increase the risk of lung cancer, but become insignificant after Bonferroni correction (OR = 0.82 [0.68, 1.00], p-value = 0.045). In addition, we noted no direct causal relationship between other risk factors and lung cancer. Neither heterogeneity nor pleiotropy was observed in this study. However, when treating the smoking behavior as the outcome, we found the increased BMI could elevate the number of cigarettes per day (beta = 0.139[0.104, 0.175], p-value = 1.99x10-14) and a similar effect was observed for the waist circumference and hip circumference. Additionally, the elevation of SBP could also marginally increase the number of cigarettes per day (beta = 0.001 [0.0002, 0.002], p-value = 0.018).<h4>Conclusion</h4>Smoking behavior might be the most direct and effective modifiable way to reduce the risk of lung cancer. Meanwhile, smoking behavior can be affected by other risk factors, especially obesity.Jie DingZhenxing TuHongquan ChenZhiguang LiuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258498 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jie Ding Zhenxing Tu Hongquan Chen Zhiguang Liu Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.
description	<h4>Background</h4>Lung cancer is the major cause of mortality in tumor patients. While its incidence rate has recently declined, it is still far from satisfactory and its potential modifiable risk factors should be explored.<h4>Methods</h4>We performed a two-sample Mendelian randomization (MR) study to investigate the causal relationship between potentially modifiable risk factors (namely smoking behavior, alcohol intake, anthropometric traits, blood pressure, lipidemic traits, glycemic traits, and fasting insulin) and lung cancer. Besides, a bi-directional MR analysis was carried out to disentangle the complex relationship between different risk factors. Inverse-variance weighted (IVW) was utilized to combine the estimation for each SNP. Cochrane's Q value was used to evaluate heterogeneity and two methods, including MR-Egger intercept and MR-PRESSO, were adopted to detect horizontal pleiotropy.<h4>Results</h4>Three kinds of smoking behavior were all causally associated with lung cancer. Overall, smokers were more likely to suffer from lung cancer compared with non-smokers (OR = 2.58 [1.95, 3.40], p-value = 2.07 x 10-11), and quitting smoking could reduce the risk (OR = 4.29[2.60, 7.07], p-value = 1.23 x 10-8). Furthermore, we found a dose-response relationship between the number of cigarettes and lung cancer (OR = 6.10 [5.35, 6.96], p-value = 4.43x10-161). Lower HDL cholesterol could marginally increase the risk of lung cancer, but become insignificant after Bonferroni correction (OR = 0.82 [0.68, 1.00], p-value = 0.045). In addition, we noted no direct causal relationship between other risk factors and lung cancer. Neither heterogeneity nor pleiotropy was observed in this study. However, when treating the smoking behavior as the outcome, we found the increased BMI could elevate the number of cigarettes per day (beta = 0.139[0.104, 0.175], p-value = 1.99x10-14) and a similar effect was observed for the waist circumference and hip circumference. Additionally, the elevation of SBP could also marginally increase the number of cigarettes per day (beta = 0.001 [0.0002, 0.002], p-value = 0.018).<h4>Conclusion</h4>Smoking behavior might be the most direct and effective modifiable way to reduce the risk of lung cancer. Meanwhile, smoking behavior can be affected by other risk factors, especially obesity.
format	article
author	Jie Ding Zhenxing Tu Hongquan Chen Zhiguang Liu
author_facet	Jie Ding Zhenxing Tu Hongquan Chen Zhiguang Liu
author_sort	Jie Ding
title	Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.
title_short	Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.
title_full	Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.
title_fullStr	Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.
title_full_unstemmed	Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.
title_sort	identifying modifiable risk factors of lung cancer: indications from mendelian randomization.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e98db1558ad140a096c7e382b05a61e6
work_keys_str_mv	AT jieding identifyingmodifiableriskfactorsoflungcancerindicationsfrommendelianrandomization AT zhenxingtu identifyingmodifiableriskfactorsoflungcancerindicationsfrommendelianrandomization AT hongquanchen identifyingmodifiableriskfactorsoflungcancerindicationsfrommendelianrandomization AT zhiguangliu identifyingmodifiableriskfactorsoflungcancerindicationsfrommendelianrandomization
_version_	1718374498580824064

Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.

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