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. 2025 Jan-Dec:32:10732748251320842.
doi: 10.1177/10732748251320842.

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

Xiao-Bo Ding  1 , Si-Yan Ren  2 , He-Zhi Wen  3 , Zhi-Bin Zhang  4 , Jia-Ang Ye  5 , Wen-Kai Pan  6 , Jia-Qi Ye  7
Affiliations

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

Xiao-Bo Ding et al. Cancer Control. 2025 Jan-Dec.

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.

Keywords: epstein-barr virus; genetic epidemiology; mendelian randomization; prostate cancer.

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Conflict of interest statement

Conflict of Interest StatementThe authors affirm that this research has been executed free from any affiliations or financial interests that might be perceived as constituting conflicts of interest. The study’s integrity is thereby ensured, with no influence from external commercial entities.

Figures

Figure 1.
Figure 1.
Two-sample Mendelian randomization analysis flow chart.
Figure 2.
Figure 2.
Mendelian randomization analysis of four EBV antibodies and prostate cancer.
Figure 3.
Figure 3.
Reverse Mendelian randomization results for four EBV antibodies and prostate cancer.
See this image and copyright information in PMC

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