title: At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer.
abstract: Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. Given that ∼50% of the global population is infected with this pathogen, there is great impetus to elucidate underlying causes that mediate progression from infection to cancer. Recent evidence suggests that H. pylori-induced chronic inflammation and oxidative stress create an environment conducive to DNA damage and tissue injury. DNA damage leads to genetic instability and eventually, neoplastic transformation. Pathogen-encoded virulence factors induce a robust but futile immune response and alter host pathways that lower the threshold for carcinogenesis, including DNA damage repair, polyamine synthesis and catabolism, antioxidant responses, and cytokine production. Collectively, such dysregulation creates a protumorigenic microenvironment within the stomach. This review seeks to address each of these aspects of H. pylori infection and to call attention to areas of particular interest within this field of research. This review also seeks to prioritize areas of translational research related to H. pylori-induced gastric cancer based on insights garnered from basic research in this field. See related review by Dalal and Moss, At the Bedside: H. pylori, dysregulated host responses, DNA damage, and gastric cancer.
authors.affiliation: Departments of Pathology, Microbiology, and Immunology and Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; and.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Hardbower
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; and Cancer Biology, and.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.affiliation: Departments of Pathology, Microbiology, and Immunology and Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; and Cancer Biology, and Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA keith.wilson@vanderbilt.edu.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
mesh_terms: D004249:DNA Damage; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology* / Q000401:mortality / Q000473:pathology
keywords: DFMO; carcinogenesis; oxidative stress