Abstract 9: Genetic and oncogenic viruses as risk factors in Egyptian breast cancer patients

Abstract Introduction: Breast cancer (BC) is a leading cause of death worldwide. Genetic factors, such as ATM, BRCA1, BRCA2, CHEK2, and PALB2 are detected in 5%-7% of women with breast cancer elevating risk of disease development. The role of environmental factors such as oncogenic viruses remained under investigation. Therefore, we aimed to investigate correlation between variations in some exons of BRCA1, BRCA2, CHEK2, and PALB2 and presence of human papillomavirus (HPV), human mammary tumor virus (HMTV), and Epstein-Barr virus (EBV) DNAs in the blood of BC patients, hoping to understand role of oncogenic viruses in cancer development Methods: Genomic DNA was extracted from 55 fresh tissues and blood samples of BC patients, as well as ten blood samples from healthy women, served as a control using Gene JET Extraction Kit (Thermo Scientific/US, Canada). PCR assay was employed to detect presence of HPV, HMTV and EBV DNAs. Additionally, variations in BRCA1, BRCA2, PALB2, and CHEK2 genes were screened using high resolution melting assays. Results: HPV and HMTV DNAs were detected in the blood of 25.5% and 23.6% BC patients, respectively, with 9% of patients exhibiting co-presence of both viruses. No viral DNAs was detected in the healthy controls. In tumor tissues, HPV DNA, HMTV DNA, and EBV DNA were detected in 47.2%, 27.2%, and 25.5% of BC patients (P=0.012). Regarding genetic analysis, variations were detected in BRCA1 25.5%, BRCA2 43.6%, PALB2 42%, and CHEK2 52.7% genes of the blood of 55 BC patients. Our results demonstrated overlapping between PALB2, CHEK2, and BRCA2 variants in BC patients. Among PALB2 carriers, 30% harbored BRCA2 variants, among CHEK2 carriers, 32% harbored BRCA2 variants. Moreover, 25% of PALB2 carriers and 18% of CHEK2 carriers presented with BRCA1 variants. Additionally, our findings revealed co-occurrence of genetic variations among BC patients. Notably, 45.4% with BRCA2 exon11 variants, exhibited variations in both PALB2 exon 4 and CHEK2 exon 10. Additionally, 43% had variations in BRCA1 exon 6, and in CHEK2 exon 10, 57% had variations in BRCA1 exon 9 and PALB2 exon 4. Results indicated an association between presence of viral DNAs and some genetic variations. Among 26 HPV-positives, 19.2% exhibited variations in exons 11 and 27 of BRCA2, and 50% had variations in PALB2 exon 4. In 15 HMTV-positives, 20% had variations in BRCA2 exon 27, and 66.7% exhibited variations in CHEK2 exon 10. Conclusion: Results suggest a potential association between genetic variations in BRCA1, BRCA2, PALB2, and CHEK2, and presence of oncogenic viruses (HPV, HMTV) in the pathogenesis of BC. Further investigations are required to confirm these observations. Data indicated a correlation between CHEK2, BRCA2, and HMTV, and between PALB2, BRCA1, and HPV. Understanding these associations, especially if present in certain exons may aid in understanding the role of oncogenic viruses and developing new markers for early detection and prognosis of disease. Citation Format: Sarah Mohamed ElSayed, Rania Abdulmonem Al Najar, Nasra Fathy Abdel Fattah, Ayman Abdel-Samie Gaber, Tarek Hashem, Wafaa Khalaf, Ahmed Basyony, Mohamed A. Eltokhy, Sahar Mohamed Radwan, Amany abdullah EL-Sharif, Samah Loutfy. Genetic and oncogenic viruses as risk factors in Egyptian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 9.