
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 28, 2025
Abstract Studies suggest a possible association between Epstein-Barr virus (EBV) infection and bladder cancer (BCa) risk, though this remains unclear. Secreted frizzled-related protein (sFRP) is also linked to BCa, with some DNA viruses potentially regulating its expression. This study used Mendelian randomization (MR) colocalization analysis explore the causal relationship EBV infection, BCa mediating role of sFRP. We first performed two-sample MR assess 5 EBV-related antibodies (AEB-IgG, EA-D, EBNA-1, VCA-p18, ZEBRA) using Finnish Consortium’s R11 dataset, validated R10. Reverse followed. For significant results, multivariable (MVMR) was applied adjust for confounding risk factors. A two-step explored potential 3 sFRPs (sFRP1, sFRP2, sFRP3) positive exposures BCa. Colocalization were conducted exposures, mediators, multiple sensitivity analyses confirming robustness results. The found that EBNA-1 (OR = 1.15, 95% CI: 1.01–1.30; p 0.039) VCA-p18 1.36, 1.13–1.64; 0.001) may increase only (P_fdr 0.006) showing effect after False Discovery Rate (FDR) correction. Consortium R10 replication yielded similar reverse did not causality. After MVMR adjusted relevant confounders, 1.40, 1.13–1.74; 0.002) still significantly increased risk. Two-step identified sFRP2 as mediator, down-regulating expression elevate suggested shared variant (nearby gene HLA-DQA1) (PPH4 65.44%). Multiple confirmed Our suggests (VCA-p18 antibody) by lowering levels. Additionally, contribute an elevated hope these findings will provide new insights future research on
Язык: Английский