Gastric cancer is the only epithelial tumor other than nasopharyngeal carcinoma (NPC) that has been shown to be associated with Epstein-Barr virus (EBV) infection. In contrast to NPC, however, only a modest fraction of gastric cancers are associated with EBV. To date, most studies that have evaluated EBV-associated gastric cancer have been modest in size, and it is unclear whether co-factors associated with EBV-positive gastric cancers differ from those associated with the more common EBV-negative tumors. To explore this area, DCEG researchers conducted a meta-analysis including 15,952 cases of gastric cancer assessed by in situ hybridization for EBV-encoded small RNA. The pooled prevalence estimate of EBV positivity was 8.7%. EBV-positive tumors were more common among males for tumors arising in the gastric cardia or corpus and for tumors in postsurgical gastric stump/remnants. Over 90% of the rare lymphoepithelioma-like carcinomas were EBV positive. To identify associations that could not be addressed in our meta-analysis, investigators conducted an individual-level pooled analysis of data for 5,081 gastric cancer cases with consistent laboratory testing for EBV. Additional findings from this evaluation included higher prevalence in young subjects, diffuse-type histology, and studies from the Americas. Multivariable aggregated analyses identified significant pair-wise interactions between sex, age, and subsite. These findings suggest that EBV-positive gastric cancer is a distinct etiologic entity.
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