Small breast cancer study finds no significant EBNA1 link to severity

A molecular study of 60 women found no statistically significant association between variations in the C-terminal region of Epstein–Barr virus nuclear antigen 1 (EBNA1) and breast cancer severity. Investigators sequenced the EBNA1 gene in biopsy samples from 30 women with EBV-positive breast lesions and compared the results with samples from 30 healthy female controls, all of whom tested negative for EBV. The analysis specifically examined whether particular EBNA1 variants were associated with pathological tumor grade.

Of the 30 participants in the breast cancer group, 29, or 97%, had invasive ductal carcinoma and one, or 3%, had ductal carcinoma in situ. Pathological classification showed that 3% of the cancers were grade I, 63% were grade II and 33% were grade III. Researchers amplified and sequenced the C-terminal region of the EBNA1 gene and conducted statistical analysis using SPSS version 25. The study identified 15 consensus single-nucleotide polymorphisms and six random mutations in the analyzed sequences.

The P-Thr EBNA1 prototype was the predominant form reported in the study population. Among patients with higher-grade tumors, P-Thr was observed in 70% and co-infection with the V-Leu variant was observed in 30%. These patterns did not show a statistically significant association with breast cancer severity. The random single-nucleotide polymorphisms likewise were not significantly associated with severity. Accordingly, the results do not support EBNA1 C-terminal variation as a marker of tumor grade in this cohort.

Phylogenetic analysis indicated that the study’s P-Thr sequences were highly similar to the EBV reference sequence NC_009334. This comparison concerns the sequences included in the study’s phylogenetic analysis, rather than establishing an effect of EBV on cancer development or clinical outcomes. The analysis was confined to a limited set of EBV-positive breast biopsy samples and used healthy, EBV-negative women as the control group.

EBNA1 plays a role in maintaining Epstein–Barr virus persistence, and the study focused on variation in its C-terminal region as a possible molecular correlate of breast cancer severity. The central result was negative: although P-Thr was the predominant prototype and P-Thr/V-Leu co-infection was more common among patients with higher-grade tumors, neither pattern was significantly linked to severity. The small sample of 60 women and the specific composition of the cancer and control groups limit the scope of the findings. Within those boundaries, the study reports no significant relationship between EBNA1 C-terminal variations and breast cancer severity.

Subject of Research: Association of EBNA1 C-terminal variants with pathological grade in breast cancer

Article Title: Association of EBV EBNA1 C-terminal variations with severity of Invasive ductal carcinoma

Article References: Khattak, A., Khan, S., Nauman, F., & Ali, I. (2026). Association of EBV EBNA1 C-terminal variations with severity of Invasive ductal carcinoma. Molecular Biology Reports, 53(1), Article 1498. https://doi.org/10.1007/s11033-026-12682-1

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12682-1

Keywords: Epstein–Barr virus, EBNA1, breast cancer, invasive ductal carcinoma, tumor grade, viral sequencing, single-nucleotide polymorphisms, molecular oncology, Association, C-terminal, variations, severity