Epstein-Barr virus is the cause of infectious mononucleosis. Many documents show EBV is associated with a variety of malignant neoplasms including nasopharyngeal carcinoma (NPC), Burkitt lymphoma, Hodgkin lymphoma, nasal T/NK cell lymphoma, and B cell-lymphoma in the immunosuppressed and gastric cancer patient. Although the global prevalence of EBV has been consistently reported in 95% of adults, the proportion of tumors associated with this virus has been reported differently in different regions (16) .
Gastric cancer is the third most common cause of cancer-related mortality and one of the most common tumors of the gastrointestinal tract worldwide(1, 2). The present work assessed the prevalence of Epstein-Barr virus in tissue samples of patients with gastric cancinoma in Ahvaz, Iran.
To date, several studies have attempted to discover the role of EBV infection in the progression of gastric cancer. EBV enters B lymphocytes in oropharyngeal lymphoid tissues. The virus then enters the gastric epithelial cells, either by the cell-to-cell contact between B lymphocytes and gastric epithelial cells or through direct entry into the gastric epithelial cells..(2)
According to the results of the study, the frequency of EBV in patients with gastric cancer in Ahwaz is 7% but not in the benign ulcer cases. The diagnosis of EBV-associated gastric cancer is confirmed by the presence of the EBNA1 gene within the gastric cancer cells and its absence in the control group cases.
The association of EBV and gastric cancer was first reported in 1990. Now, various studies from different countries show EBV is related to 10% of gastric cancer patients. EBV-associated GC differs in various geographical regions, e.g, 6.4 % in China, 8.1 % in Mexico, 19.5 % in German, 5.6% in Korea, 12% in the United States, 8.5% in France, 13% in Colombia, and 11.3% in Brazil. (16). The results of this study compared with previous studies in Iran. The frequency of EBV in patients with gastric cancer in Tehran, Sari, and Kerman was reported 7%, 3%, 11%, respectively. (16–18)
Since the prevalence of EBV-associated gastric cancer is lower in areas with a high incidence of gastric cancer and in areas with a low prevalence of gastric cancer is more and because Ahvaz is the region with a high incidence of Gastric cancer. (19, 20) In contrast, Amoueian reported a very high prevalence (62%) of EBVassociated GC in the Northeast of Iran compared with other areas of the World and showed an important correlation between EBV infection and incidence of Gastric cancer. Some investigators checked EBV in GCs and suggested that there are ethnic differences in tumor virology and pathogenesis. (21)
EBV-associated gastric cancer varies in different countries, it seems that economic conditions are not an important variable for EBV associated gastric cancer because low and high frequencies were found in both developed and developing countries (16). Therefore, these variations in EBV-associated occurrence of GC in different areas may represent epidemiological and clinicalopathological factors; dietary habits and genetic.; dietary habits and genetic. (21) We should consider that the low number of positive cases in our study might be the reason for the insignificant result in the analysis (P-value = 0.318).
EBV encoded genes in EBV associated gastric carcinoma as follows: EBNA-1, LMP1, LMP2, EBERs and, miRNAs reported in the majority of tumor cells and EBNA2, 3A, 3B, 3C, LP and not reported in most tumor cells of GC. EBNA-1 targets a single copy highly conserved gene and is important for the long-term maintenance of the virus in dividing cells. The possible contribution of EBV to GC pathogenesis is largely unknown. It has been suggested that EBV may be associated with the majority of the cases, including those diagnosed as EBV negative (EBNA1) or EBER negative by a mechanism of hit-and-run. Early during oncogenesis, viral genes are necessary for the initiation of disease. Gradually, the viral genome is lost to avoid the immune response and host mutations accumulate in the proto-oncogenic cell. (15) Based on this hypothesis, the negation of the EBER gene in our study can be justified. In the same way, Lee and co-workers in the study from Korea showed that the presence of EBV was indicated in 3 samples (3.30%) by EBER-ISH, 26 samples (28.57%) by Nested PCR, and 3 samples (3.30%) by EBER PCR.(15) In this way, Lee and colleagues found that EBV was detected in 4 of 40 cases (10%)of gastric carcinoma whereas LMP1, was negative. (22)
In most studies, sex differences favor men, but not were some studies have shown a significant relationship between sex and EBVaGC. (23) In this study, EBV-associated gastric cancer was seen more in men, but according to the statistical analysis of the results, not was a significant relationship found between sex and EBVaGC-. (P-value > 0.99) (Table 1).
The mean age for patients with EBV-positive gastric carcinomas was 65.8 years. However, in the present study, the highest incidence of EBV-positive gastric carcinomas was in the age group of 70–79 years (4.2%) but there is no significant statistical was seen between age and EBV-positive gastric carcinomas (P-value = 0.282) (Table 1). These findings are in accord with results reported by other studies investigating from Portugal (24), Russian(25), Mexico, and Several cities in Iran. (17, 18, 20) However, several studies were shown a tendency to involvement at lower age (Kazakhstan and Colombia). (26, 27) or higher age (Mexico and Malaysian). (28, 29)
The division of gastric cancer is as follows: 1- Adenocarcinoma 2- Lymphoma 3- Stromal sarcoma 4- Liposarcoma 5- Squamous cell carcinoma. More than 95% of gastric cancers are adenocarcinomas (17, 30). Laurén divided the histology of gastric cancer into two groups, i.e., the intestinal- type and the diffuse- type; later, the indeterminate type was included to describe uncommon histology. Most studies showed the intestinal type to be the most common, followed by the diffuse and then indeterminate type.(31) Several constant clinical-pathological features were seen in EBV associated gastric cancer such as moderately to the poorly differentiated type of gastric cancer and predisposition to upper stomach (16). As shown in Table 2 in the present study all patients had adenocarcinoma (65% intestinal and 35% diffuse type). The prevalence of EBVaGC in diffuse type gastric carcinoma was more in our study, a fact which was seen in most studies of Latin America (28, 32) and some countries in Asia such as Korea (33), China, (34) and India (35). Abdirad and co-workers in a study from Iran showed the proportion of EBV-GC cases in diffuse- type was higher than intestinal- type (P > 0.05). (20)
Some studies have demonstrated a better prognosis of EBVaGC than for Gastric carcinoma with EBV negative. Studies reported that there are also many prognostic factors in GC that affect survival, such as grade, lymphovascular invasion, resection type, and performance status. In this research, most cases of EBV have been observed in grade 1 cancers(36).
The present study indicates that the prevalence of EBV-associated gastric carcinoma in Iran is low. Differences in the occurrence of EBV-associated gastric carcinoma in different countries can represent epidemiological factors and dietary trends. Regarding the significant mortality rate of GC, EBV should be more considered in this group in the different geographic areas to receive appropriate specific treatment for EBV.