title: Epstein Barr virus: a prime candidate of breast cancer aetiology in Sudanese patients.
abstract: Breast cancer is the commonest cancer in Sudanese women. Reported genetic alterations in the form of mutations in tumor suppressors are low in frequencies and could not explain the peculiarities of the diseases including its focal nature. Potential contributors disease aetiology include oncogenic viruses such as Epstein-Barr virus (EBV), an established culprit of nasopharyngeal carcinoma, one of the most frequent cancers in Sudan.In this study, DNA was extracted from malignant tissue samples and healthy tumour-free tissue from the same breast. Polymerase chain Reaction (PCR) was used to amplify two genes encoding for EBV viral proteins. The presence of Epstein-Barr virus and its cellular localization was confirmed by in situ hybridization (ISH) for Epstein-Barr encoded small RNAs (EBERs). Given the reported low frequency of mutations in BRCA1 and BRCA2 in Sudanese breast cancer patients, the methylation status of six tumor suppressor genes was investigated using methylation specific PCR. EBV genome was detected in 55.5% (n = 90) of breast cancer tissues as compared to 23% in control tissue samples (p = 0.0001). Using ISH, EBV signal was detected in all 18 breast cancer biopsies examined while all five normal breast tissue biopsies tested were negative for EBV. Of six tumour suppressor genes investigated BRCA1, BRCA2, and p14 appeared to be under strong epigenetic silencing.In conclusion, we present evidence of a strong association between EBV and breast carcinoma in Sudanese patients, and considerable epigenetic silencing of tumor suppressors that may likely be an outcome or an association with viral oncogenesis.
authors.forename: Zeinab A
authors.initials: ZA
authors.lastname: Yahia
authors.forename: Ameera Am
authors.initials: AA
authors.lastname: Adam
authors.forename: Magdeldin
authors.initials: M
authors.lastname: Elgizouli
authors.forename: Ayman
authors.initials: A
authors.lastname: Hussein
authors.forename: Mai A
authors.initials: MA
authors.lastname: Masri
authors.forename: Mayada
authors.initials: M
authors.lastname: Kamal
authors.forename: Hiba S
authors.initials: HS
authors.lastname: Mohamed
authors.forename: Kamal
authors.initials: K
authors.lastname: Alzaki
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Elhassan
authors.forename: Kamal
authors.initials: K
authors.lastname: Hamad
authors.affiliation: Institute of Endemic Diseases (IEND) Unit of Disease and Diversity, University of Khartoum Medical Campus, P,O, Box 102, Khartoum, Sudan. mibrahim@iend.org.
authors.forename: Muntaser E
authors.initials: ME
authors.lastname: Ibrahim