Epstein-Barr Virus and Gastric Cancer

Abstract

Chronic inflammation, triggered by infectious agents, has a key role in the development of malignancies (Aggarwal et al. 2006). The estimated total of infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of the global cancer burden (Parkin 2006). Among the principal agents, Helicobacter pylori and Epstein-Barr virus (EBV) are two common and widely disseminated pathogens throughout the world, and account for 5.5% and 1% of total malignancies, respectively (Parkin 2006). H. pylori has been classified by the International Agency for Research on Cancer (IARC) as a class I carcinogen, i.e., a clear and unquestionable causative agent for gastric cancer (GC). EBV was isolated in 1964 from Burkitt’s lymphoma (Epstein et al. 1964), which was first described in 1958 to be unique endemic jaw tumors in equatorial African (Burkitt 1958). Shortly after that, Old and colleagues discovered the link between EBV and epithelial malignancies. They incidentally observed that patients with nasopharyngeal cancer (NPC), a prevalent epithelial malignancy in southern China, are associated with a significantly elevated antibody titer to EBV (Old et al. 1966). Later studies demonstrated that EBV is closely linked to carcinogenicity in Burkitt’s lymphoma, non-Hodgkin lymphoma in immunosuppressed subjects, sinonasal angiocentric T-cell lymphoma, Hodgkin lymphoma, and NPC. EBV is now considered to be a group I carcinogen for the above-mentioned cancers by the IARC (IARC 1997). The first hint of an association between EBV and GC came in 1990 from a case of undifferentiated lymphoepithelioma-like gastric carcinoma (LELC), in which EBV was detected using polymerase chain reaction (PCR) (Burke et al. 1990). Subsequently, EBV has been found in most cases of the rare tumor subtype (LELC) and a considerable portion of common gastric adenocarcinomas (Osato and Imai 1996; Rugge and Genta 1999; Takada 2000). Unique morphologic and phenotypic features have been reported for EBV-associated GC (EBVaGC). These divergent clinicopathologic characteristics raise the possibility that EBV-positive and -negative GCs adopt different carcinogenetic pathways. However, the evidence concerning the link between EBV and GC, unlike the situation for H. pylori, is considered to be