Exploring the Causal Relationship Between Atopic Dermatitis and Malignancies: A Comprehensive Observational and Genetic Study

<u><b><i></i></b></u> <u><b><i>Background:</i></b></u> Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation. The global rise in the incidence of both AD and cancer suggests a potential link through shared immune-inflammatory pathways.<u><b><i>Objective:</i></b></u> This study aimed to investigate the causal relationship between AD and multiple cancer types and to explore potential underlying biological mechanisms.<u><b><i>Methods:</i></b></u> A two-sample Mendelian randomization (MR) analysis was conducted using data from a genome-wide association study of 6,224 AD patients. Seventeen cancer types were assessed. Additionally, expression quantitative trait loci analysis, pathway enrichment, and survival analyses were performed.<u><b><i>Results</i>:</b></u> MR analysis identified a significant causal relationship between AD and the risk of esophageal cancer (odds ratio [OR] = 0.88, <i>P</i> = 0.0247) as well as colorectal cancer (OR = 0.94, <i>P</i> = 0.0154). Subsequent research revealed differential expression between tumor and normal tissues, with pathway enrichment highlighting immune processes. No survival association was found in esophageal cancer, but <i>MFN2</i> and <i>SIPA1</i> expression levels could affect outcomes in colorectal cancer.<u><b><i>Conclusion:</i></b></u> This study provides evidence for a protective causal relationship between AD and the risks of esophageal and colorectal cancers. Immune and inflammatory pathways may mediate this link.