Abstract
Abstract
Breast cancer is the most common female malignancy globally. Being a multifactorial disease, the study investigated germline variants in tumour suppressor genes (TSGs) and viral DNA detection in breast cancer and their associations. In this case-control study, 640 women (320 breast cancer patients and 320 healthy individuals) were screened for germline variants in TSGs (
BRCA1
,
BRCA2
,
TP53
and
PTEN
) using Sanger sequencing. Furthermore, PCR-based detection of HPV, EBV and HCMV was performed. Associations were determined using multivariable logistic regression and false discovery rate correction was performed using the Benjamini-Hochberg procedure. Age > 50 years (aOR = 2.42, 95% CI: 1.73–3.40;
p
p
BRCA1
-EBV-HCMV co-occurrence pattern (2.87-fold enrichment,
q
= 0.0049). A family history of breast cancer was significantly associated with P/LP variant carrier status for
BRCA1
(aOR = 8.06, 95% CI: 1.66–39.23;
q
= 0.047). After age adjustment and FDR correction, only
BRCA2
P/LP variants were significantly associated with HPV positivity (aOR = 20.69, 95% CI: 2.95-148.51;
q
= 0.049). HER2-positive tumours were less frequent among EBV-positive patients than EBV-negative patients (
p
= 0.0175). Exploratory pathway enrichment analysis identified significant enrichment of the KEGG breast cancer pathway (FDR = 5.89 × 10⁻⁸) among the analysed virus-host interacting genes. The findings demonstrate the co-occurrence and statistical associations between TSG variants and viral detection in breast cancer, warranting further functional studies to clarify their biological significance.