From infection to tumor: genetic evidence of viral antibody immune response’ role in urologic cancer development

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BACKGROUND: Urologic tumors are among the most common malignancies worldwide, and the association between chronic infections and the risk of developing these tumors has garnered significant attention. However, traditional observational studies are prone to confounding factors, making it challenging to establish a clear causal relationship. METHOD: This study employs a two-sample bidirectional Mendelian randomization analysis, utilizing genetic data on antibody levels and urologic tumors obtained from GWAS databases. The inverse variance weighted (IVW) method was used to estimate causal relationships, while MR-Egger and MR-PRESSO methods were applied for sensitivity analyses to assess horizontal pleiotropy and heterogeneity. RESULT: The results showed that antibody levels associated with various viral infections were significantly correlated with the risk of developing urologic tumors. For example, antibodies related to cytomegalovirus IgG and Epstein-Barr virus (EBV) were found to have complex associations with the risk of prostate cancer, bladder cancer, and testicular cancer. Some antibodies, such as those related to Varicella zoster virus, were associated with a reduced risk of clear cell renal carcinoma. Additionally, sensitivity analyses suggested the potential presence of horizontal pleiotropy in bladder and testicular cancers. CONCLUSION: Through Mendelian randomization analysis, we revealed a potential causal relationship between antibody immune responses and urologic tumors. These findings provide new evidence for the role of chronic infections in the pathogenesis of urologic tumors, suggesting that prevention and treatment strategies targeting related pathogens, such as vaccination and antiviral therapies, could offer new avenues for the prevention and management of urologic cancers.

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