Exploring the Impact of Neuroticism on Lung Cancer Risk: Insights From Mediated Mendelian Randomization.

OBJECTIVE

This study aimed to explore the potential association between neuroticism and lung cancer.

METHODS

We conducted analyses on publicly accessible aggregated data from genome-wide association studies (GWAS) that included individuals of European descent. The objective was to identify single nucleotide polymorphisms (SNPs) significantly associated with neuroticism and utilize them as instrumental variables in a two-sample Mendelian randomization framework to evaluate the gender-specific causal link between neuroticism and lung cancer risk. We applied four statistical methods: Inverse variance weighting (IVW), weighted median, MR-Egger regression, and weighted mode. Our analysis also considered the mediating effect of educational attainment on this relationship.

RESULTS

We selected 67 SNPs associated with neuroticism at genome-wide significance levels from GWAS datasets. Our primary findings using IVW suggest a notable increase in lung cancer risk associated with neuroticism across the general population (odds ratio [OR] = 1.175; 95% confidence interval [CI] 1.020-1.354, p = 0.026). Gender-specific analysis revealed that neuroticism posed a slight but significant risk increase in men (OR = 1.006; 95% CI 1.000-1.012, p = 0.045) and women (OR = 1.005; 95% CI 1.002-1.009, p = 0.002), with findings corroborated by the additional statistical methods. Further, evidence from both observational and Mendelian randomization analyses suggests that genetically predicted neuroticism is causally associated with a modestly increased risk of incident lung cancer, with ∼17% of this effect mediated by educational attainment.

CONCLUSIONS

The results from this Mendelian randomization study provide robust evidence supporting a potential association between neuroticism and an increased risk of lung cancer. This association appears more pronounced in men than women. Additionally, educational level serves as a mediator in the nexus between these conditions, suggesting that interventions aimed at increasing educational attainment might mitigate some of the risk neuroticism poses for developing lung cancer.