Does Epstein-Barr Virus Contribute to Breast Cancer Risk Worldwide? A Systematic Review and Meta-Analysis.

[INTRODUCTION] Breast cancer (BC) is the most common cancer among women worldwide, accounting for over 2.3 million new cases annually. Recent evidence suggests Epstein-Barr virus (EBV) may play a role in its pathogenesis. Given EBV's known oncogenic potential, this study investigates the prevalence and possible role of EBV in BC pathogenesis.

[METHODS] Random-effects meta-analyses were conducted to estimate raw proportions and risk ratio (RR), with 95% confidence intervals (CIs). Heterogeneity was assessed using I². Statistical significance was set at P < .05. Analyses were performed in R 4.2.3 RESULTS: Our meta-analysis included 57 studies, comprising a total of 5,133 BC tissues to analyze the presence of EBV. Our analysis revealed a prevalence of 25% (95% CI: 21%-30%) of EBV in BC tissues. In the analysis by continent, Europe, Africa, and Oceania showed a similar proportion of 33%. Regarding the risk of EBV in BC tissues compared to healthy controls, the analysis identified a statistically significant difference, presenting higher risk of EBV in the BC group (RR: 3.35; P < .001). South America showed the highest and significant RR of 12.34 (P = .007) among the continents. Subgroup analysis by income revealed that the low-income-group exhibited the highest EBV prevalence (44%; 95% CI: 28%-61%). According to the subtype BC analysis, triple-negative BC exhibited the highest EBV prevalence (30%; 95% CI: 19%-44%).

[CONCLUSION] This meta-analysis underscores the global prevalence of EBV in BC and highlights a potential association between EBV presence and breast cancer. Further standardized, prospective studies using robust detection methods, including paired tissue analyses, are needed to confirm these observations and to clarify the possible role of EBV in breast tumorigenesis.