title: Inflammation and Barrett's carcinogenesis.
abstract: Barrett's esophagus (BE) is one of the most common premalignant lesions in which normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. Esophageal adenocarcinoma (EA) develops through progression from BE to low- and high-grade dysplasia (LGD/HGD) and to adenocarcinoma. It is widely accepted that inflammation can increase cancer risk, promoting tumor progression. Therefore, inflammation is regarded as the seventh hallmark of cancer. In recent years, the inflammation-cancer connection of Barrett's carcinogenesis has been intensively studied, unraveling genetic abnormalities. Besides genetic alterations, inflammation is also epigenetically linked to loss of protein expression through transcriptional silencing via promoter methylation. Key mediators linking inflammation and Barrett's carcinogenesis include reactive oxygen species (ROS), NFκB, inflammatory cytokines, prostaglandins, and specific microRNAs (miRNAs). Therefore, the decipherment of molecular pathways that contain these and novel inflammatory key mediators is of major importance for diagnosis, therapy, and prognosis. The detailed elucidation of the signaling molecules involved in Barrett's carcinogenesis will be important for the development of pharmaceutical inhibitors. We herein give an overview of the current knowledge of the inflammation-mediated genetic and epigenetic alterations involved in Barrett's carcinogenesis. We highlight the role of oxidative stress and deregulated DNA damage checkpoints besides the NFκB pathway.
authors.affiliation: Department of Pathology, Otto-von-Guericke University Magdeburg, Germany. Albert.Roessner@med.ovgu.de
authors.forename: A
authors.initials: A
authors.lastname: Poehlmann
authors.forename: D
authors.initials: D
authors.lastname: Kuester
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
authors.forename: T
authors.initials: T
authors.lastname: Guenther
authors.forename: A
authors.initials: A
authors.lastname: Roessner
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D018450:Disease Progression; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D004942:Esophagitis, Peptic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species