**7. Summary and conclusions**

Novel molecular classifications and meta-analyses identified Epstein-Barr virus (EBV) as a distinct etiological agent for gastric cancer. An important characteristic of EBV-associated gastric carcinoma (EBVaGC) is the difference in incidence in Asia and the Americas. Specific EBV genes such as EBERs, EBNAs, BARTs and LMP are the most actively expressed in EBVaGC, and variations in its sequences might be associated with phylogeographic diversity of EBV strains across the world. Polymorphisms at BamHI W1/I1 boundary region and XhoI RFLPs at exon 1 of the LMP-1 gene have been found in healthy donors reflecting the mixing of different ethnic populations in the Americas. However, this is not the case for gastric cancer, since almost all types of EBVaGC studied harbor exclusively the western genotypes (subtype D and kept XhoI site). These findings propose that a disrupted coevolution between a pathogen and its healthy population might contribute to a phylogeographic origin of disease. DNA methylation and cellular and viral microRNAs play an emerging role in the pathogenesis of EBVaGC.
