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

Frontiers in Oncology

Yuzhuo Wang²  Xiaoxia Wei²  Xu Zhang²  Xikang Fan²  Xiangxiang Jiang²  Yanqian Huang²  Mengmeng Ji²  Lin Xu³  Rong Yin³  Jing Xu⁴  Lingbin Du⁵  Juncheng Dai⁶  Dong Hang⁶  Zhibin Hu⁶  Meng Zhu⁶  Guangfu Jin⁶  Hongxia Ma⁷ 

[1] Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China;Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China;Department 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, China;Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China;Research Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing, China;

关键词: lung cancer;    neuroticism;    genetic risk;    prospective analysis;    Mendelian randomization study;   

DOI  :  10.3389/fonc.2022.836159

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown