Causal relationship between circulating cytokines and follicular lymphoma: a two-sample Mendelian randomization study

Area of Science:

• Hematology
• Immunology
• Genetics

Background:

• Follicular lymphoma (FL) is an incurable B-cell neoplasm.
• The association between circulating cytokines and FL development is suggested but not causally confirmed.

Purpose of the Study:

• To confirm the causal relationship between circulating cytokine levels and FL risk using Mendelian randomization.
• To identify specific cytokines that may influence FL development.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis utilizing genome-wide association study summary data.
• Statistical methods included inverse variance weighted (IVW), weighted median (WME), and MR-Egger.
• Sensitivity analyses were performed to assess heterogeneity and pleiotropy.

Main Results:

• Four cytokines showed a causal link with FL: C-X-C motif chemokine ligand 5 (CXCL5), interleukin-15 receptor A (IL15RA), interleukin-20 (IL20), and neurotrophin-3 (NT-3).
• CXCL5, IL15RA, and IL20 were associated with decreased FL risk (inverse relationship).
• NT-3 was associated with increased FL risk (positive relationship).

Conclusions:

• CXCL5, IL15RA, and IL20 exhibit anti-protective effects against FL.
• NT-3 demonstrates a protective effect on FL.
• These findings offer insights into FL pathogenesis and potential cytokine-based therapeutic targets.