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.
BackgroundThe oncogenic potential of Epstein-Barr virus (EBV) in breast cancer is being increasingly recognized. Despite some controversies regarding such role, new evidence is suggesting a culpability of EBV in breast cancer, particularly in Africa where the virus has been originally associated with causation of several solid and hematological malignancies. One example is a report from Sudan implicating EBV as a prime etiologic agent for an aggressive type of breast cancer, where nearly 100% of tumor tissues were shown to carry viral signatures. To get a broader view on such association, other nearby countries should be investigated. The present study aims to determine the prevalence and possible associations of the virus in Eritrean breast cancer patients.MethodsDetection of EBV genome using primers that target Epstein Barr Encoded RNA (EBER) gene and Latent Membrane Protein-1 (LMP-1) gene sequences was performed by polymerase chain reaction (PCR) on DNA samples extracted from 144 formalin fixed paraffin embedded breast cancer tissues and 63 non-cancerous breast tissue as control group. A subset of PCR positive samples was evaluated for EBER gene expression by in situ hybridization (ISH). Expression of Latent Membrane Protein-2a (LMP2a) was also assessed by immunohistochemistry in a subset of 45 samples.ResultsBased on PCR results, EBV genome signals were detected in a total of 40 samples (27.77%) as compared to controls (p-value = 0. 0031) with a higher sensitivity when using the EBER primers. Five out of the 14 samples stained by EBER-ISH 35.71% were positive for the virus indicating the presence of the viral genome within the tumor cells. Of those stained for IHC 7 (15.55%) were positive for LMP2a showing low viral protein frequency.ConclusionsBased on these findings it can be concluded that EBV in Eritrea is associated with a smaller subset of tumors, unlike neighboring Sudan, thus pointing to possible differences in population predisposition and diseases epidemiology.
The aim of this report is to determine frequencies and associations of p53 codon 72 arg/pro polymorphism with different types of cancer in Sudan. p53 codon72 arg/pro polymorphism distribution and allele frequencies in 264 samples of different types of cancers were investigated using PCR. The results were compared to 235 normal controls. The results indicated significant differences in frequency and genotype association between different types of cancers. Breast carcinoma patients most prominently showed excess of homozygous arg genotype as compared to controls with an Odd ratio (OR) of 19.44, 95 %CI: 6.6-78.3, P < 0.0001. Less prominently cervical cancer showed genotype effect of 2.4 OR, 95 %CI: 1.12-5.33, P = 0.015, while esophageal cancer had an OR of 0.57, 95 %CI: 0.23-1.42, P = 0.1. In Burkitt's lymphoma, however, in contrast the homozygous arg accounted for only 6.9 %, (OR 0.18, 95 %CI: 0.02-0.89, P = 0.018). We concluded that p53 arg/pro polymorphism has different pattern of frequency in different types of cancer among Sudanese patients, indicating perhaps different etiology and biology of these tumours.
Objectives:To study the epidemiology, clinical features, staging, etiology and pathology of nasopharyngeal cancer in Sudan.Study design:This is a retrospective study.Setting:Ear, Nose and Throat Department Khartoum Teaching Hospital, Khartoum City, Sudan.Subjects and methods:Patients suspected to have nasopharyngeal cancer were assessed during the period March 2004 to May 2010. Data from confirmed cases was obtained; it included clinical and epidemiological information.Results:Three hundred and eighty five cases were studied. Bimodal age distribution of the disease was noted with two peaks, one at 15–19 years and one at 50–54 years. The male to female ratio was 2.6:1 and a distinct geographical distribution of the disease was noted, with clustering of cases in the towns of Dilling, Kadogli and the surrounding rural area of the Nuba Mountains. These areas in the Western States were reported to be of high background radiation due to naturally produced radioactive uranium. The Nuba tribe headed the list among other tribes, demonstrating a clear ethnic predilection.Sixty-eight cases presented at stage IV. There was a predominance of Type II (15.58%) and Type III (65.97%). Patients were treated by neoadjuvant chemoradiotherapy.Conclusions:NPC is an important form of cancer in Sudan. Some tribes are significantly more affected than others. Patients present with advanced disease. Environmental and genetic factors need further studies. Screening at risk populations that aim at early diagnosis and management of patients is recommended.
Objectives: The aim of this study is to detect Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC) biopsies of Sudanese patients using EBV-encoded RNA (EBER) in Situ hybridization (EBER-ISH). Study Design: This is a descriptive cross-sectional study conducted at the National Center for ENT diseases and Head and Neck Surgery and the Institute of Endemic Diseases, University of Khartoum, Khartoum City, Sudan. Subjects and Methods: Biopsies from 43 patients with nasopharyngeal carcinoma were examined for the presence of Epstein-Barr virus using EBER-ISH. Ten normal samples were used to assess the presence of the virus in non cancer tissues. Results: Fifty three samples were examined for the presence of the virus by EBER-ISH, 43 biopsies were NPC and ten were normal. Histologically the cases were, 20 (46.5%), 20 (46.5%) and 3 (7%) of the biopsies were classified as WHO types II, III and mixed type II and III, respectively; there were no cases of type I NPC. All nasopharyngeal carcinoma biopsies (100%) were positive for EBER1 in almost all carcinoma cells with focal and intense dark-blue staining limited to the nucleus; no hybridization was observed in the cytoplasm. No hybridization was observed in all ten non cancer tissues. Conclusion: All NPC cells are clearly EBV-infected. The virus is located in the nucleus of the tumour cells. The presence of Epstein-Barr virus in normal nasopharyngeal epithelia is not a common event.
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