title: Pathogenesis of Gastric Cancer.
abstract: Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. GC is a heterogeneous disease and the endpoint of a long multistep process largely influenced by Helicobacter pylori infection, genetic susceptibility, and environmental factors. In a subset of GC cases, infection with the Epstein-Barr virus (EBV) may also be involved. The development of GC is the consequence of the accumulation of multiple epi/genetic changes during the patient's lifetime that will result in oncogenic activation and/or tumor suppressor pathways' inactivation. This review will focus on the most recent updates on the characterization of the molecular phenotypes of sporadic and hereditary GC. This article will also update the most recent findings on the relationship between H. pylori infection and stem cells at the origin of GC. The understanding of the molecular genetics underlying gastric carcinogenesis is of paramount importance to identify novel potential targets for the development of screening and prognostic markers that can be clinically valuable for the management of GC patients and for the design of clinical trials.
authors.affiliation: Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
authors.forename: Ceu
authors.initials: C
authors.lastname: Figueiredo
authors.affiliation: Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Costa
authors.affiliation: Department of Pathology, Veterans Administration Hospital (NIMTS), Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Karameris
authors.affiliation: Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Machado
mesh_terms: D004781:Environmental Exposure; D020031:Epstein-Barr Virus Infections / Q000150:complications; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
keywords: Epstein-Barr virus; Helicobacter pylori; hereditary gastric cancer; molecular profiles; stem cells