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

Background: 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. Objective: This study aimed to investigate the causal relationship between AD and multiple cancer types and to explore potential underlying biological mechanisms. Methods: 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. Results: MR analysis identified a significant causal relationship between AD and the risk of esophageal cancer (odds ratio [OR] = 0.88, P = 0.0247) as well as colorectal cancer (OR = 0.94, P = 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 MFN2 and SIPA1 expression levels could affect outcomes in colorectal cancer. Conclusion: 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.