The causal relationship between multiple cardiovascular diseases and glioblastoma: A Mendelian randomization study

Area of Science:

• Neuro-oncology
• Cardiovascular Medicine
• Genetic Epidemiology

Background:

• Observational studies suggest a link between glioblastoma (GBM) and cardiovascular diseases (CVDs), but causality is unproven.
• Understanding the etiological relationship between GBM and CVDs is crucial for developing preventative strategies and treatments.

Purpose of the Study:

• To investigate the potential causal relationship between 18 different cardiovascular diseases and the risk of developing glioblastoma.
• To determine if CVDs act as protective factors against GBM using a robust genetic approach.

Main Methods:

• A 2-sample Mendelian randomization (MR) study utilizing publicly available genome-wide association study data.
• Instrumental variables were single-nucleotide polymorphisms strongly associated with 18 CVDs (exposures), with GBM as the outcome.
• Inverse variance weighted method was the primary analysis, supported by MR-Egger, weighted median, and weighted mode methods, alongside comprehensive sensitivity analyses.

Main Results:

• All 18 investigated CVDs showed a statistically significant causal association with a reduced risk of GBM (P < 0.05).
• Genetically predicted CVDs were consistently associated with lower GBM risk (odds ratio < 1), indicating a protective effect.
• Sensitivity analyses confirmed the robustness of findings, ruling out significant heterogeneity, pleiotropy, and confirming causal direction.

Conclusions:

• This MR study provides strong evidence that various cardiovascular diseases are causally linked to a decreased risk of glioblastoma.
• The findings suggest shared underlying biological mechanisms between CVDs and GBM.
• These results offer novel insights into GBM etiology and potential avenues for future research and therapeutic interventions.