Causal relationships between inflammatory factors and multiple myeloma: A bidirectional Mendelian randomization study

Area of Science:

• Immunology
• Genetics
• Oncology

Background:

• Inflammatory factors play a role in multiple myeloma (MM) onset and progression.
• Distinguishing causal relationships from effects is challenging due to complex feedback loops.

Purpose of the Study:

• To elucidate the causal relationships between C-reactive protein (CRP), inflammatory regulators, and MM using a bidirectional Mendelian randomization (MR) analysis.

Main Methods:

• Summary-level data from genome-wide association studies (GWASs) for CRP, cytokines, and MM (372,617 UK Biobank participants) were analyzed.
• Inverse-variance weighted (IVW) method was primary, with MR-Egger, weighted median, and MR-PRESSO for sensitivity analyses.

Main Results:

• Higher levels of monocyte-specific chemokine-3, vascular endothelial growth factor, interleukin-10, and interleukin-7 were associated with increased MM risk.
• Lower levels of tumor necrosis factor-beta were strongly associated with increased MM risk.
• Genetically predicted MM was linked to increased interleukin-17 levels.

Conclusions:

• This study provides genetic evidence for the causal relationships between specific inflammatory factors and MM.
• Targeted interventions focusing on these inflammatory factors may offer potential strategies for mitigating MM risk.