The conundrum of the Epstein-Barr virus-associated gastric carcinoma in the Americas
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Gonzalo Carrasco-Avino1,2, Ismael Riquelme3,4, Oslando Padilla5, Miguel Villaseca4, Francisco R. Aguayo1,6 and Alejandro H. Corvalan1,7,8
1Advanced Center for Chronic Diseases (ACCDIS), Pontificia Universidad Catolica de Chile, Santiago, Chile
2Department of Pathology, Faculty of Medicine, Universidad de Chile, Santiago, Chile
3Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de la Frontera, Temuco, Chile
4Department of Pathology, Universidad de la Frontera, Temuco, Chile
5Department of Public Health, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
6Department of Basic and Clinical Oncology, Faculty of Medicine, Universidad de Chile, Santiago, Chile
7UC-Center for Investigational Oncology (CITO), Pontificia Universidad Catolica de Chile, Santiago, Chile
8Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
Alejandro H. Corvalan, email: [email protected]
Keywords: gastric cancer, Epstein-Barr virus, americas, molecular classification, phylogeographic diversity
Received: December 20, 2016 Accepted: May 29, 2017 Published: June 15, 2017
Epstein-Barr virus-associated gastric carcinoma shows a higher prevalence in the Americas than Asia. We summarize all studies of Epstein Barr virus-associated gastric carcinoma in the Americas, focusing on host characteristics, environmental associations and phylogeographic diversity of Epstein-Barr virus strains. In the Americas, the prevalence of Epstein Barr virus-associated gastric carcinoma is 11.4%, more frequent in males and portray predominantly diffuse-type histology. EBERs, EBNAs, BARTs and LMP are the highest expressed genes; their variations in healthy individuals may explain the phylogeographic diversity of Epstein-Barr virus across the region. Gastric cancer cases harbor exclusively the western genotype (subtype D and kept Xho I site), suggesting a disrupted co-evolution between the pathogen and its host. Epstein-Barr virus-associated gastric carcinoma molecular subtype cases from The Cancer Genome Atlas display PIK3CA gene mutations, amplification of JAK2, PD-L1 and PD-L2 and CpG island methylator phenotype, leading to more extensive methylation of host and viral genomes than any other subtypes from the study. Environmental conditions include negative- and positive- associations with being firstborn child and smoking, respectively. A marginal association with H. pylori has also been reported. Lymphoepithelioma-like carcinoma is associated with Epstein Barr virus in 80%–86% of cases, most of which have been included as part of Epstein Barr virus-associated gastric carcinoma series (prevalence 1.1%–7.6%). Whether these cases represent a variant of Epstein-Barr virus-associated gastric carcinoma is discussed. We propose novel research strategies to solve the conundrum of the high prevalence of Epstein-Barr virus-associated gastric carcinoma in the Americas.
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