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.

Presence of Human Papillomavirus and Epstein-Barr Virus in Breast Cancer Biopsies as Potential Risk Factors

“…This result is below the values reported in other studies conducted at a global level, which range from 21-55% of EBV DNA positivity, depending on the type of technique employed for viral DNA detection 4,19,40 . In works using some type of PCR, as in our study, low infection rates were detected, as in the trial by Xue, et al in 2003, who, using BZLF1 gene-specific reverse transcriptase PCR, detected viral DNA in 17% of breast cancer cases, and the work by Yahia, in 2014, who detected 11% of EBV DNA positivity in breast cancer cases using PCR with EBNA-1 gene-specific primers 41,42 . In Latin America, very few studies have assessed the presence of EBV in breast cancer, and have reported a rate of infection ranging from 6-31% 31,43 .…”

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

“…2016; 11(3):e34806. (11,18,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). Table 1 shows a summary of the EBV-DNA positive subjects according to nationality, types of sample, and kinds of control tissue in the 20 selected studies.…”

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“…Also, PCR of LMP1 gene, was detected by Yahia et al, 2014 in 53.3% of BC patients and in 24% of the control group. It was also in concordance to Aboulkassim et al, 2015.…”