Causal association between Parkinson's disease and cancer: a bidirectional Mendelian randomization study

Area of Science:

• Neuroscience
• Oncology
• Genetic Epidemiology

Background:

• Observational studies suggest a correlation between Parkinson's disease (PD) and various cancers, but causality remains uncertain.
• Investigating the causal relationship between PD and cancer is crucial for understanding disease mechanisms and potential interventions.

Purpose of the Study:

• To explore the potential causal links between Parkinson's disease and 14 types of cancer using Mendelian randomization (MR).
• To determine the directionality of the causal relationship between PD and cancer.

Main Methods:

• Bidirectional two-sample Mendelian randomization (TSMR) analysis was performed using genetic variants associated with PD and cancer.
• Summary statistics were obtained from large-scale genomic consortia.
• Inverse variance weighted (IVW) method was the primary analysis, supported by sensitivity analyses and FDR correction for multiple testing.

Main Results:

• Parkinson's disease showed a suggestive causal effect in decreasing the risk of gastric cancer (OR=0.936) and colorectal cancer (OR=0.955).
• PD was suggestively associated with an increased risk of breast cancer (OR=1.043).
• No evidence supported a causal link from cancer to PD, although skin cancer showed a suggestive inverse association with PD (OR=0.913).

Conclusions:

• Mendelian randomization analysis provides evidence for unidirectional, suggestive causal relationships between Parkinson's disease and specific cancers.
• These findings contribute to understanding the complex interplay between PD and cancer, highlighting the need for further mechanistic research.