Irritability and risk of lung cancer: a Mendelian randomization and mediation analysis

There is no research to prove the association between irritability and lung cancer, our study performed a Mendelian randomization (MR) approach to elucidate the causal relationship of irritability with lung cancer risk.

Genome-wide association studies (GWAS) data of irritability, lung cancer and gastroesophageal reflux disease (GERD) were downloaded from a public database for two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with irritability and GERD were selected as instrumental variables (IVs). Inverse variance weighting (IVW) and weighted median method were used to analyze causality.

There is an association between irritability and lung cancer risk (OR_IVW = 1.01, 95% CI = [1.00, 1.02], P = 0.018; OR_{weighted median} = 1.01, 95% CI = [1.00, 1.02], P = 0.046), and GERD might account for about 37.5% of the association between irritability and lung cancer.

This study confirmed the causal effect between irritability and lung cancer through MR analysis, and found that GERD played an essential mediating role in this relationship, which can partly indicate the role of the "inflammation-cancer transformation" process in lung cancer.