Association between inflammatory cytokines and prostate cancer: a bidirectional Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Oncology
• Immunology

Background:

• Prostate cancer (PCa) is a significant global health concern.
• The role of inflammatory cytokines in PCa etiology requires further elucidation.
• Mendelian randomization (MR) offers a robust approach to investigate causal relationships.

Purpose of the Study:

• To investigate the potential causal links between 91 inflammatory cytokines and prostate cancer (PCa) using a bidirectional two-sample MR analysis.
• To identify novel cytokine biomarkers associated with PCa risk and progression.

Main Methods:

• A bidirectional two-sample Mendelian randomization (MR) analysis was performed.
• Inverse variance weighted (IVW) was the primary method, complemented by weighted median (WM) and MR Egger.
• Sensitivity analyses included Cochran's Q test and MR-Egger intercept test for pleiotropy.

Main Results:

• Elevated levels of C-C motif chemokine 20 (CCL20), C-C motif chemokine 23 (CCL23), fibroblast growth factor 19 (FGF19), fibroblast growth factor 23 (FGF23), and interleukin-6 (IL-6) showed a positive causal association with PCa.
• Interleukin-6 (IL-6) demonstrated the strongest positive effect, followed by CCL20 and FGF23.
• A negative causal relationship was observed between PCa and interleukin-22 receptor subunit alpha-1 (IL22RA1) levels, suggesting decreased IL22RA1 is linked to PCa development.

Conclusions:

• Findings suggest that increased levels of CCL20, CCL23, FGF19, FGF23, and IL-6 are associated with a higher risk of developing PCa.
• Evidence supports a causal role for decreased IL22RA1 in PCa pathogenesis.
• These cytokines represent potential therapeutic targets for PCa prevention and treatment.