Causal relationships between circulating inflammatory cytokines and diffuse large B cell lymphoma: a bidirectional...

Area of Science:

• Immunology and Oncology
• Genetic Epidemiology

Background:

• Diffuse large B cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin lymphoma.
• Inflammatory cytokines are implicated in DLBCL pathogenesis, but causal links are obscured by feedback loops.

Purpose of the Study:

• To investigate the potential causal relationships between DLBCL and specific inflammatory cytokines using a bidirectional Mendelian randomization approach.
• To identify upstream inflammatory drivers of DLBCL and downstream effects of DLBCL on cytokine levels.

Main Methods:

• A bidirectional Mendelian randomization study utilizing genetic variants from genome-wide association studies.
• Data sourced from 8293 European participants for cytokine-associated genetic variants and 1010 DLBCL cases from the FinnGen consortium.
• Primary analysis employed the inverse-variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and MR-PRESSO sensitivity analyses.

Main Results:

• Elevated Monokine induced by interferon gamma (MIG/CXCL9) and interferon gamma-induced protein 10 (IP-10/CXCL10) levels showed suggestive associations with increased DLBCL risk (IVW method).
• DLBCL was suggestively associated with increased levels of macrophage colony-stimulating factor (M-CSF), tumor necrosis factor beta (TNF-β), and TNF-related apoptosis-inducing ligand (TRAIL).

Conclusions:

• This study provides evidence supporting a causal role for specific inflammatory cytokines in DLBCL development.
• MIG/CXCL9 and IP-10/CXCL10 are identified as potential upstream risk factors for DLBCL.
• DLBCL may lead to elevated levels of M-CSF, TNF-β, and TRAIL, suggesting potential therapeutic targets for DLBCL prevention and treatment.