Causal association between oxidative stress and lymphomas: A two-sample Mendelian randomization study

Objectives To explore the causal associations between oxidative stress markers and the occurrence of various types of lymphomas. Methods This two-sample Mendelian randomization (MR) study employed summary data from genome-wide association studies of oxidative stress markers and various lymphoma types. Analysis was conducted using the inverse variance weighted, with confirmation using the weighted median, weighted mode, and MR-Egger regression methods. Heterogeneity, horizontal pleiotropy, outliers, and robustness were tested using the Cochran Q, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods. Results Genetically predicted myeloperoxidase (MPO) was causally associated with follicular lymphoma (odds ratio (OR) = 1.33, P = 0.0173). Uric acid showed a causal link to diffuse large B-cell lymphoma (DLBCL) (OR = 1.003, P = 0.043). Glutathione peroxidase (GPX) was associated with follicular lymphoma (OR = 1.16, P = 0.033). Catalase (CAT) was inversely associated with non-Hodgkin lymphoma (NHL) (OR = 0.8921), non-follicular lymphoma (OR = 0.8755), and follicular lymphoma (OR = 0.8364) (all P < 0.05). Glutathione-S transferase (GST) was inversely associated with NHL (OR = 0.9248) and follicular lymphoma (OR = 0.8313) (all P < 0.05). Heterogeneity was noted for uric acid and DLBCL, but no pleiotropy was detected; after outlier removal, the association with uric acid was non-significant. Conclusions The findings suggest causal relationships between oxidative stress markers and lymphoma risk, notably MPO and GPX with follicular lymphoma, and inverse associations for GST and CAT with different lymphoma types. Limitations include heterogeneity for some markers, requiring further validation.