Association between different types of lung cancer and neurodegenerative diseases: A two-sample Mendelian randomization study

Previous observational studies demonstrated that lung cancer and both Alzheimer disease (AD) and Parkinson disease (PD) may be related. However, the results of different studies are still controversial, possibly due to differences in the types of lung cancer examined. To date, no research has discussed it further yet. In this study, Mendelian randomization (MR) analysis was employed to investigate the relationship between different types of lung cancer and neurodegenerative diseases. We extracted data sets related to the exposure (lung cancer) and outcomes (AD/PD) from the Integrative Epidemiology Unit open Genome-Wide Association Study project. Then, we carried out two-sample MR analyses to explore the connection between lung cancer and both AD and PD. We also conducted sensitivity analyses on positive results from the MR analysis to make sure the results were accurate. Our two-sample MR analyses revealed that lung squamous cell carcinoma (LUSC) is negatively related to AD (OR = 0.935, 95% CI [0.892-0.980], P = .005). According to the sensitivity and heterogeneity analyses, no heterogeneity (P = .223) and pleiotropy (P = .548) were observed in this positive result. Thus, the findings were reliable. The IVW findings suggested that LUSC and PD did not significantly correlate (OR = 0.920, 95% CI [0.778-1.089], P = .332). Similarly, there was no obvious connection between lung adenocarcinoma and AD (OR = 0.968, 95% CI [0.915-1.025], P = .270) and PD (OR = 0.981, 95% CI [0.851-1.130], P = .787), according to IVW results. Results of two-sample MR analyses revealed that LUSC and a decreased risk of AD may be related.