Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study.

Purpose: Marginal zone lymphoma (MZL) is a rare subtype of non-Hodgkin lymphoma, and its diagnosis primarily relies on pathological biopsy. The study aims to investigate the causal relationships between 41 inflammatory cytokines and MZL using a two-sample bidirectional Mendelian randomization (MR) approach, providing new insights and methodologies for rapid differential diagnosis and treatment strategies.

Methods: Causal associations between 41 inflammatory cytokines and MZL were examined using genetic variant data from two large-scale genome-wide association studies. The inverse variance weighting method was employed, and multiple sensitivity analyses, including MR-Egger, weighted median, simple model, and weighted model methods, were conducted to strengthen the robustness of the findings.

Results: Elevated levels of MIG and IL-10 were associated with an increased risk of MZL (MIG: OR = 1.57, p = 0.035; IL-10: OR = 1.69, p = 0.021), while higher B-NGF levels exhibited a protective effect (OR = 0.46, p = 0.027). Reverse MR analysis revealed a negative correlation between MZL and IFN-γ levels (OR = 0.97, p = 0.015).

Conclusions: MIG, IL-10, B-NGF, and IFN-γ are potential biomarkers and therapeutic targets for MZL. IFN-γ likely acts as a downstream molecule in MZL pathogenesis, offering novel insights into MZL-related research, clinical diagnosis, and treatment strategies.