A Bidirectional Mendelian Randomization Study on the Causal Relationship Between Epstein-Barr Virus Antibodies and Prostate Cancer Risk

Abstract

Objectives This study aims to examine the correlation between four distinct Epstein-Barr virus (EBV) antibodies (EA-D, EBNA-1, VCA-p18, and ZEBRA) and the likelihood of developing prostate cancer (PCa) using the Mendelian Randomization (MR) technique. The primary objective is to determine whether a causal relationship exists between these EBV antibodies and prostate cancer. Methods Genome-wide association study (GWAS) data for EBV antibodies were sourced from the UK Biobank cohort, and prostate cancer data were obtained from the PRACTICAL consortium, which includes 79148 cases and 61106 controls. Univariable Mendelian Randomization (MR) analysis was conducted to evaluate the associations, while reverse Mendelian Randomization was employed to assess causality. Additionally, Multivariable Mendelian Randomization analysis was performed to identify independent risk factors. Results Univariable MR analysis revealed significant associations between EBV EA-D (OR = 1.084, 95% CI = 1.012-1.160, IVW_ P = 0.021) and EBNA-1 (OR = 1.086, 95% CI = 1.025-1.150, IVW_ P = 0.005) antibodies and an increased risk of prostate cancer. Reverse MR analysis did not establish a causal relationship. Multivariable MR analysis identified the EBV EBNA-1 antibody as an independent risk factor for prostate cancer (OR = 1.095, 95% CI = 1.042-1.151, IVW_ P = 0.00036). Conclusion The study highlights the association between EBV antibody levels, particularly EBNA-1, and prostate cancer risk, suggesting EBNA-1 as an independent risk factor. Future research is needed to elucidate the biological pathways linking EBV antibody levels to prostate cancer. These insights could be instrumental in developing targeted prevention strategies and therapeutic interventions for prostate cancer.