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

Area of Science:

• Oncology
• Genetics
• Biochemistry

Background:

• Oxidative stress is implicated in cancer development, but its causal role in lymphoma pathogenesis remains unclear.
• Understanding the relationship between oxidative stress markers and lymphoma risk is crucial for prevention and treatment strategies.

Purpose of the Study:

• To investigate the potential causal associations between genetically predicted oxidative stress markers and the risk of developing various lymphoma subtypes.
• To utilize a two-sample Mendelian randomization approach to assess these relationships, leveraging large-scale genome-wide association study data.

Main Methods:

• A two-sample Mendelian randomization study design was employed.
• Summary statistics from genome-wide association studies for oxidative stress markers and lymphoma types were utilized.
• Inverse variance weighted method was the primary analysis, with weighted median, weighted mode, and MR-Egger regression used for confirmation and robustness checks.

Main Results:

• Genetically predicted myeloperoxidase (MPO) showed a causal association with an increased risk of follicular lymphoma (OR=1.33).
• Glutathione peroxidase (GPX) was also associated with follicular lymphoma (OR=1.16).
• Catalase (CAT) and glutathione-S transferase (GST) demonstrated inverse associations with non-Hodgkin lymphoma (NHL) and follicular lymphoma, suggesting a protective effect.

Conclusions:

• The study suggests potential causal links between specific oxidative stress markers (MPO, GPX) and increased risk of follicular lymphoma.
• Inverse associations were observed for CAT and GST with certain lymphoma types, indicating a potential protective role.
• Further research is needed to validate these findings, particularly addressing observed heterogeneity in some associations.