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

Xiaoxia Wei,Dong Hang,Jing Xu,Juncheng Dai,Xiangxiang Jiang,Yanqian Huang,Hongxia Ma,Lingbin Du,Xu Zhang,Xikang Fan,Lin Xu,Guangfu Jin,Mengmeng Ji,Rong Yin,Yuzhuo Wang,Meng Zhu,Zhibin Hu

doi:10.3389/fonc.2022.836159

Abstract

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.

Highlights

Neuroticism is a personality trait that reflects relative stability to experience negative emotions
Of the 364,451 participants included in the analysis, 1573 developed incident lung cancer during a median follow-up period of 7.13 years
A genetically predicted neuroticism was associated with an increased risk of lung cancer (OR inverse-variance weighted (IVW)=1.10, 95% confidence interval (CI): 1.03-1.17), and the association was stable in sensitivity analyses using other Mendelian randomization (MR) methods (Figure 1)

Summary

Introduction

Neuroticism is a personality trait that reflects relative stability to experience negative emotions. Neuroticism is one of the major dimensions of the Five-Factor Model of personality [1], and it is one of the most studied psychological dispositions because of its relevance ranging from normal to abnormal emotional functioning [2]. Evidence linking regarding neuroticism to lung cancer risk, is scarce and inconsistent. Most of the previous studies were limited by the lack of strict adjustment for confounding variables (e.g., smoking and alcohol use), a short follow-up period or small numbers of lung cancer cases. The exact association between neuroticism and lung cancer still needs to be determined in well-designed prospective studies with large samples. It remains undetermined whether neuroticism affects the risk of lung cancer. We performed complementary observational and Mendelian randomization (MR) analyses to investigate the association between neuroticism and lung cancer risk

Methods

Results

Conclusion