Mendelian Randomization Combined with Bioinformatics Revealed Specific Allergy-Mediated Protective Mechanisms Against Renal Cell Carcinoma.

There is evidence that allergic diseases are associated with carcinogenesis. According to translational and epidemiological data, it appears that different cancer types yield different associations. We investigated the relationship between allergic diseases and 28 cancers by Mendelian randomization. Quantitative trait locus analysis was utilized to determine genes expressed in kidney tissue that were affected by allergy-related loci. We further explored the underlying molecular mechanism between allergic diseases and renal cell carcinoma (RCC) with bioinformatics. Of the 28 cancers, evidence suggested that allergies specifically suppressed kidney cancer. Seventy single nucleotide polymorphisms associated with allergic diseases affected the expression of 134 genes in kidney tissue. These 134 genes were enriched in immune-related pathways represented by the major histocompatibility complex class II antigen presentation pathway. Among them, seven core genes were significantly positively correlated with T helper 2 cells. Allergic diseases specifically suppressed RCC through multiple immune pathways. Among them, the major histocompatibility complex class II antigen presentation pathway and T helper 2 cells were the most critical. Our study sheds light on the underlying mechanisms of allergic diseases and RCC and provides therapeutic targets for RCC. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-025-00229-6.