Exploring the relationship between Alzheimer's disease and colorectal/breast cancers using SEER database, Mendelian...

Area of Science:

• Gerontology and Oncology
• Neurodegenerative Diseases
• Cancer Epidemiology

Background:

• Alzheimer's disease (AD) and cancer are prevalent age-related diseases with a poorly understood relationship.
• Existing research has not fully elucidated the clinical or causal links between AD and various cancers.

Purpose of the Study:

• To examine clinical characteristics of AD patients with cancer using SEER data.
• To investigate the causal relationship between AD and cancers via Mendelian randomization (MR).
• To identify shared underlying mechanisms through transcriptomic profiling.

Main Methods:

• Utilized SEER database for clinical data and survival analysis (Kaplan-Meier curves).
• Performed two-sample MR analysis using GWAS data with multiple methods (IVW, MR-Egger, weighted median).
• Analyzed transcriptomic data (GEO database) for AD, colorectal cancer (CRC), and breast cancer (BC), identifying differentially expressed genes (DEGs) and performing functional enrichment (GO, KEGG).

Main Results:

• Survival analysis of 42,768 AD patients showed varied prognoses based on age, ethnicity, tumor site, and treatment.
• MR analysis indicated a positive causal link between AD and CRC, and a weak inverse link between AD and BC.
• Shared DEGs between AD and BC were enriched in amino acid and organic acid transport, and vesicle docking.
• Shared DEGs between AD and CRC involved synaptic function and protein catabolism.
• KEGG analysis suggested shared synaptic vesicle cycle pathway between AD and BC.

Conclusions:

• Significant heterogeneity exists among cancer patients who died from AD.
• AD is causally linked to increased CRC risk and potentially decreased BC risk.
• Shared mechanisms may involve amino acid transport, myo-inositol import, and synaptic vesicle cycling.