Investigating bidirectional causality between prostate cancer and inflammatory factors: A 2-sample Mendelian...

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Growing evidence suggests bidirectional relationships between inflammatory cytokines and prostate cancer (PCa).
• However, the causal link between genetic susceptibility to inflammatory cytokines and PCa remains underexplored.

Purpose of the Study:

• To investigate the causal inferences and directional effects between 91 inflammatory cytokines and PCa using a bidirectional Mendelian randomization (MR) approach.
• To identify specific inflammatory factors that may influence the incidence and progression of PCa.

Main Methods:

• Utilized a bidirectional Mendelian randomization (MR) study design.
• Employed inverse variance weighted (IVW) as the primary statistical method, with MR-Egger regression, weighted median, MR-PRESSO, and simulation extrapolation for enhanced accuracy.
• Sensitivity analyses included MR-Egger and Cochran Q statistic to assess heterogeneity.

Main Results:

• Identified a causal relationship between fms-related tyrosine kinase 3 ligand (Flt3L), monocyte chemotactic protein 2 (MCP2), and MCP4, and the incidence of PCa.
• Flt3L and MCP4 were suggested as potential risk factors for PCa, while MCP2 may be a favorable factor.
• Reverse analysis indicated PCa is correlated with elevated levels of adenosine deaminase, axin-1, C-X-C motif chemokine ligand 6, Flt3L, interleukin (IL)-24, and IL-33, suggesting their involvement in PCa progression.

Conclusions:

• This study highlights the causal role of specific inflammatory factors in the development of PCa.
• Flt3L and MCP4 may represent novel risk factors, and MCP2 a potential protective factor for PCa.
• Several inflammatory markers are implicated in the downstream pathways of PCa progression, warranting further investigation.