May obesity increase the risk of lymphoma? Insights from genetic evidence

Lymphoma poses a significant public health challenge with complex subtypes. While obesity and adipokines have been linked to lymphoma, causal relationships remain unclear. This study uses Mendelian randomization (MR) to systematically assess these associations. Two-sample MR analyzed genetic data from genome-wide association studies to evaluate causal links between obesity, adipokines (adiponectin, leptin, and resistin), and lymphoma subtypes (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Hodgkin lymphoma, and other unspecified types of non-Hodgkin lymphoma). Primary analysis used inverse variance weighted (IVW), supported by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses (MR-Egger regression, Cochran’s Q test, MR-PRESSO, leave-one-out) and linkage disequilibrium score regression (LDSC) ensured robustness. IVW revealed obesity positively associated with follicular lymphoma (OR = 1.352, 95% CI: 1.095–1.670, <i>p</i> = 0.005) and other unspecified types of non-Hodgkin lymphoma (OR = 1.297, 95% CI: 1.050–1.603, <i>p</i> = 0.016). No significant links were found between adipokines and lymphoma. Sensitivity analyses confirmed no heterogeneity or pleiotropy. Obesity may independently increase lymphoma risk, unrelated to adipokines. These findings highlight new risk factors, urging further research into pathological mechanisms and biomarkers.