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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Frontiers Media S.A.
2022-02-01
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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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