Ferritin and Iron Levels Inversely Associated With Lymphoma Risk: A Mendelian Randomization Study

Background: Current knowledge on iron's role in lymphoma development is very limited, with studies yielding inconsistent findings. To address this gap, we conducted a rigorous two-sample mendelian randomization study, aiming to elucidate the potential associations between iron storage and the risk of developing lymphoma. Methods: This study leveraged extensive genetic data derived from a comprehensive genome-wide association study (GWAS) comprising 257,953 individuals. The primary objective was to pinpoint single-nucleotide polymorphisms (SNPs) that are significantly associated with iron storage. Subsequently, this genetic information was analyzed in conjunction with summary-level data pertaining to lymphoma cases and controls, sourced from the IEU open GWAS project, which included a sample size of 3,546 lymphoma cases and 487,257 controls. To evaluate the relationship between iron storage and lymphoma risk, an inverse variance-weighted method with random effects was employed, complemented by rigorous sensitivity analyses. Results: Genetic predisposition to high ferritin and serum iron status was causally associated with lower odds of lymphoma. Ferritin exhibited an odds ratio (OR) of 0.777 (95% confidence interval (CI): 0.628- 0.961, P = 0.020), indicating 22.3% reduced odds of lymphoma associated with a one standard deviation increase in ferritin levels. Similarly, serum iron demonstrated an OR of 0.776 (95% CI: 0.609- 0.989, P = 0.040), corresponding to 22.4% decreased odds of lymphoma for a one standard deviation increase in serum iron. Conclusions: This study suggests that individuals with genes linked to higher iron storage levels have a lower risk of developing lymphoma, but further research is necessary before making any clinical recommendations.