Human betaretrovirus (HBRV), homologous to mouse mammary tumor virus (MMTV), and human breast cancer: a significant epidemiological association.

Abstract

Background: Breast cancer is the most commonly diagnosed cancer globally. The potential role of oncogenic viruses, particularly Human Betaretrovirus (HBRV, formerly MMTV-LV/HMTV), in the pathogenesis of breast cancer has been a subject of research for decades. However, studies investigating this association have produced conflicting results. This systematic review and meta-analysis aim to assess the prevalence of HBRV in breast cancer cases and evaluate its potential association with breast cancer.

Methods: A systematic literature search was conducted in MEDLINE, Web of Science, Scopus, and EMBASE following PRISMA guidelines. Studies assessing HBRV prevalence in breast cancer patients and case-control studies investigating its association with breast cancer risk were included. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality, and meta-analysis was performed using RevMan 5.1. Heterogeneity was assessed using the I² statistic, and subgroup analyses were conducted based on detection methods, sample types, and geographic regions.

Results: The literature search identified a total of 45 studies that were deemed suitable for inclusion in the systematic review. 26 studies were used in the subsequent meta-analysis. The initial meta-analysis revealed a significant association between HBRV and breast cancer (OR = 4.92, 95% CI: 4.00-6.04, p < 0.00001) but exhibited high heterogeneity (I² = 82%). After excluding an outlier, heterogeneity was significantly reduced (I² = 22%), with a revised OR of 11.95 (95% CI: 8.78-16.25, p < 0.00001 ). Subgroup analysis demonstrated variation in detection methods, with Nested PCR (OR = 19.15) and Frozen tissue samples (OR = 18.00) showing the strongest associations. Geographic analysis indicated the highest odds in North America (OR = 24.75), followed by Europe (OR = 15.02).

Conclusion: This meta-analysis suggests strong epidemiological evidence supporting an association between HBRV infection and human breast cancer, and is consistent with a possible etiological role. However, variability in study methodologies and geographic differences warrant further investigation through standardized, large-scale studies to confirm these findings and explore potential mechanisms of viral oncogenesis in breast cancer.