This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Infection with Helicobater pylori (H. pylori) is one of the critical steps that triggers a cascade of events leading to gastric cancer. However, little is know about the molecular characterization of these pathological stages. After infection, the normal gastric epithelium becomes the focus of an inflammatory response characterized by the infiltration of immun cells without the loss of the gastric architecture (non-atrophic gastritis, NAG). NAG progresses to multifocal atrophic gastritis (MAG) with loss of gastric glands and appearance of fibrotic tissue. Finally MAG progresses to intestial metaplasia (MAG-IM) in which the gastric epithelium acquires phenotypic and fuctional characteristics of the intestinal absortive and mucus cells. MAG-IM progresses to dysplasia and finally to cancer. It is accepted that acute and chronic inflammation are essential players of the tissue damage induced by H. pylori. This inflammatory process is mediated, among other things by a milieu of cytokines produced in response to the infection. Our previous work has identified single nucleotide polymorphims (SNP) that are associated to a differential inflammatory response in African Americans and Caucasians in both gastritis and prostate cancer. However, considering the complexity of the inflammatory process, we think that many more SNPs in many genes may be associated with this response. We propose to run a whole genome genotyping (660K SNPs) in patients at the different stages of the gastric inflammatory cascade in order to establish a pattern of markers associated with the disease. I addition, a gene expression profile will be determined at each inflammatory stage. Something very unique to our proposal is the study of the evolution of these genetic patterns (SNPs and gene expression). For this we have access to a cohort of patients that have been followed for more than 15 years and from whom we have gastric tissue at several time points. We want to verify the information obtained with the human gastric samples using knockout mice models and in vitro systems with the gastric cell line AGS with overexpressing or lacking specific genes. The results of this proposal will allow the early identification of individual with higher risk of develiong advenced gastric disease and those who would benefit with treatment.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR021970-07
Application #
8360450
Study Section
Special Emphasis Panel (ZRR1-CR-B (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
7
Fiscal Year
2011
Total Cost
$195,160
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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