Exploring causal correlations between inflammatory cytokines and colorectal cancer: A 2-sample Mendelian...

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Colorectal cancer (CRC) poses a significant global health challenge.
• Previous studies on inflammatory cytokines and CRC risk have yielded inconsistent findings.
• Understanding these relationships is crucial for developing targeted prevention and treatment strategies.

Purpose of the Study:

• To investigate the causal relationship between specific inflammatory cytokines and the risk of colorectal cancer.
• To differentiate the roles of cytokines in colon versus rectal cancer development.
• To leverage Mendelian randomization to overcome limitations of observational studies.

Main Methods:

• A 2-sample Mendelian randomization (MR) analysis was performed.
• The primary analytical approach was the inverse variance weighted (IVW) method.
• Robustness of findings was assessed using MR-Egger, weighted median, and weighted mode analyses.

Main Results:

• Elevated levels of interleukin (IL)-16, vascular endothelial growth factor (VEGF), and MIG were associated with increased rectal cancer risk.
• Higher macrophage colony-stimulating factor (M-CSF) levels showed a potential protective association with colon cancer.
• Reverse MR analysis indicated associations between rectal cancer and IL-1b, IL-1ra, IL-5, IL-9, and TNF-a, and colon cancer with FGF-Basic.

Conclusions:

• This study provides novel evidence supporting a causal role for specific inflammatory cytokines in colorectal cancer development.
• Findings highlight distinct cytokine profiles associated with colon and rectal cancers.
• The results warrant further investigation into cytokine-targeted therapies for CRC.