Genetically Predicted Levels of Circulating Inflammatory Cytokines and the Risk of Hodgkin Lymphoma: A Two-sample Mendelian Randomization Study

Abstract Although epidemiological and observational studies link inflammation to the occurrence and progression of Hodgkin lymphoma, the causal relationship between circulating Inflammatory cytokines Levels and Hodgkin lymphoma remains unknown. To investigate the effects of genetically predicted circulating inflammatory cytokine levels on Hodgkin lymphoma, we conducted a two-sample Mendelian randomization (MR) study. Summary-level data of genetic variants associated with circulating cytokines were included from a meta-analysis of genome-wide association studies (GWASs) of 8,293 Finns. Data on Hodgkin lymphoma were obtained from UK BioBank(360 cases and 36078 noncases). Inverse-variance weighted analysis, weighted-median analysis, and MR-Egger regression were conducted in this Mendelian randomization analysis. Sensitivity analyses were conducted to confirm the accuracy and robustness of our results. 197 genetic variants with genome-wide significance (P < 5 × 10 − 8) associated with 26 circulating cytokines were used as IVs. It was clear from the validation analysis that none of the 26 circulating inflammatory cytokines was associated with Hodgkin lymphoma risk. Our study systematically assesses the effect of circulating cytokines on Hodgkin lymphoma risk, and inflammatory cytokines are not associated with Hodgkin lymphoma risk. However, the exact underlying biological mechanism warrants further investigation.