Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses

BackgroundIt remains undetermined whether neuroticism affects the risk of lung cancer. Therefore, we performed complementary observational and Mendelian randomization (MR) analyses to investigate the association between neuroticism and lung cancer risk.MethodsWe included 364,451 UK Biobank participa...

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Main Authors: Xiaoxia Wei, Xiangxiang Jiang, Xu Zhang, Xikang Fan, Mengmeng Ji, Yanqian Huang, Jing Xu, Rong Yin, Yuzhuo Wang, Meng Zhu, Lingbin Du, Juncheng Dai, Guangfu Jin, Lin Xu, Zhibin Hu, Dong Hang, Hongxia Ma
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.836159/full
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author Xiaoxia Wei
Xiangxiang Jiang
Xu Zhang
Xikang Fan
Mengmeng Ji
Yanqian Huang
Jing Xu
Rong Yin
Yuzhuo Wang
Meng Zhu
Meng Zhu
Meng Zhu
Lingbin Du
Lingbin Du
Juncheng Dai
Juncheng Dai
Guangfu Jin
Guangfu Jin
Lin Xu
Zhibin Hu
Zhibin Hu
Dong Hang
Dong Hang
Hongxia Ma
Hongxia Ma
Hongxia Ma
author_facet Xiaoxia Wei
Xiangxiang Jiang
Xu Zhang
Xikang Fan
Mengmeng Ji
Yanqian Huang
Jing Xu
Rong Yin
Yuzhuo Wang
Meng Zhu
Meng Zhu
Meng Zhu
Lingbin Du
Lingbin Du
Juncheng Dai
Juncheng Dai
Guangfu Jin
Guangfu Jin
Lin Xu
Zhibin Hu
Zhibin Hu
Dong Hang
Dong Hang
Hongxia Ma
Hongxia Ma
Hongxia Ma
author_sort Xiaoxia Wei
collection DOAJ
description BackgroundIt remains undetermined whether neuroticism affects the risk of lung cancer. Therefore, we performed complementary observational and Mendelian randomization (MR) analyses to investigate the association between neuroticism and lung cancer risk.MethodsWe included 364,451 UK Biobank participants free of cancer at baseline. Neuroticism was ascertained using the 12-item of Eysenck Personality Inventory Neuroticism Scale. Multivariable Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Two-sample MR analysis was carried out with summary genetic data from UK Biobank (374,323 individuals) and International Lung Cancer Consortium (29,266 lung cancer cases and 56,450 controls). Furthermore, we calculated a polygenic risk score of lung cancer, and examined the joint-effect and interaction between neuroticism and genetic susceptibility on lung cancer risk.ResultsDuring a median follow-up of 7.13 years, 1573 lung cancer cases were documented. After adjusting for smoking and other confounders, higher neuroticism was associated with an increased risk of lung cancer (HR per 1 SD=1.07, 95% CI: 1.02-1.12). Consistently, MR analysis suggested a causal effect of neuroticism on lung cancer risk (OR IVW=1.10, 95% CI: 1.03-1.17). Compared to individuals with low neuroticism and low PRS, those with both high neuroticism and high PRS had the greatest risk of lung cancer (HR=1.82, 95%CI: 1.51-2.20). Furthermore, there was a positive additive but no multiplicative interaction between neuroticism and genetic risk.ConclusionsOur findings suggest that neuroticism is associated with an elevated risk of incident lung cancer, which is strengthened by the genetic susceptibility to lung cancer. Further studies are necessary to elucidate underlying mechanisms.
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spelling doaj.art-bc08f1e131444515aeea6cedf0a976c02022-12-21T23:44:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.836159836159Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization AnalysesXiaoxia Wei0Xiangxiang Jiang1Xu Zhang2Xikang Fan3Mengmeng Ji4Yanqian Huang5Jing Xu6Rong Yin7Yuzhuo Wang8Meng Zhu9Meng Zhu10Meng Zhu11Lingbin Du12Lingbin Du13Juncheng Dai14Juncheng Dai15Guangfu Jin16Guangfu Jin17Lin Xu18Zhibin Hu19Zhibin Hu20Dong Hang21Dong Hang22Hongxia Ma23Hongxia Ma24Hongxia Ma25Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, ChinaJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaDepartment of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, ChinaInstitute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaResearch Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing, ChinaBackgroundIt remains undetermined whether neuroticism affects the risk of lung cancer. Therefore, we performed complementary observational and Mendelian randomization (MR) analyses to investigate the association between neuroticism and lung cancer risk.MethodsWe included 364,451 UK Biobank participants free of cancer at baseline. Neuroticism was ascertained using the 12-item of Eysenck Personality Inventory Neuroticism Scale. Multivariable Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Two-sample MR analysis was carried out with summary genetic data from UK Biobank (374,323 individuals) and International Lung Cancer Consortium (29,266 lung cancer cases and 56,450 controls). Furthermore, we calculated a polygenic risk score of lung cancer, and examined the joint-effect and interaction between neuroticism and genetic susceptibility on lung cancer risk.ResultsDuring a median follow-up of 7.13 years, 1573 lung cancer cases were documented. After adjusting for smoking and other confounders, higher neuroticism was associated with an increased risk of lung cancer (HR per 1 SD=1.07, 95% CI: 1.02-1.12). Consistently, MR analysis suggested a causal effect of neuroticism on lung cancer risk (OR IVW=1.10, 95% CI: 1.03-1.17). Compared to individuals with low neuroticism and low PRS, those with both high neuroticism and high PRS had the greatest risk of lung cancer (HR=1.82, 95%CI: 1.51-2.20). Furthermore, there was a positive additive but no multiplicative interaction between neuroticism and genetic risk.ConclusionsOur findings suggest that neuroticism is associated with an elevated risk of incident lung cancer, which is strengthened by the genetic susceptibility to lung cancer. Further studies are necessary to elucidate underlying mechanisms.https://www.frontiersin.org/articles/10.3389/fonc.2022.836159/fulllung cancerneuroticismgenetic riskprospective analysisMendelian randomization study
spellingShingle Xiaoxia Wei
Xiangxiang Jiang
Xu Zhang
Xikang Fan
Mengmeng Ji
Yanqian Huang
Jing Xu
Rong Yin
Yuzhuo Wang
Meng Zhu
Meng Zhu
Meng Zhu
Lingbin Du
Lingbin Du
Juncheng Dai
Juncheng Dai
Guangfu Jin
Guangfu Jin
Lin Xu
Zhibin Hu
Zhibin Hu
Dong Hang
Dong Hang
Hongxia Ma
Hongxia Ma
Hongxia Ma
Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses
Frontiers in Oncology
lung cancer
neuroticism
genetic risk
prospective analysis
Mendelian randomization study
title Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses
title_full Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses
title_fullStr Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses
title_full_unstemmed Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses
title_short Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses
title_sort association between neuroticism and risk of lung cancer results from observational and mendelian randomization analyses
topic lung cancer
neuroticism
genetic risk
prospective analysis
Mendelian randomization study
url https://www.frontiersin.org/articles/10.3389/fonc.2022.836159/full
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