The burden of gastric adenocarcinoma is unevenly distributed, with several Asian and Latin American countries having particularly high incidence rates. Although chronic infection with Helicobacter pylori is the primary cause of this cancer, environmental and host cofactors modify the course of infection and determine whether infected individuals develop cancer. Due to the lack of adequate screening strategies and consequent late diagnosis, trends in mortality are similar to incidence, making this neoplasia the third leading cause of cancer death worldwide. The International Agency for Research on Cancer predicts that there will be no reduction in gastric cancer cases until at least 2030 due to population growth and aging. H. pylori-related gastric carcinogenesis is a multi-step process and mucosal lesions of intestinal metaplasia (IM) and dysplasia confer increased risk of progression. Therefore, case-control studies of these premalignant lesions may provide insights into cancer etiology and inform risk stratification. In addition, biomarkers to identify high-risk individuals are needed for early detection and curative treatment. Accordingly, we propose a 2-year study of 10,000 Chilean adults undergoing upper gastrointestinal endoscopy for clinical or screening purposes to identify 600 subjects with advanced premalignant lesions (i.e., incomplete-type IM, complete-type IM with extension to gastric corpus and dysplasia) for informative comparisons with 600 controls with non-atrophic gastritis, a benign histologic change apparent in most H. pylori infected individuals. As an additional case group, 300 individuals with newly diagnosed gastric cancer will be recruited from the same clinics. For a 4-month pilot phase, we plan to recruit 1550 patients undergoing endoscopy and 10 patients with gastric cancer. This multidisciplinary project will simultaneously evaluate bacterial, host and environmental factors towards a better understanding of gastric cancer etiology that may guide future efforts for prevention and control. We will explore risk factors that have been insufficiently studied, such as various hormones, H. pylori genomics, non- H. pylori gastric microbiota, and other parasitic infections. We will also evaluate potential noninvasive screening markers, including pepsinogens, hormones, miRNAs and DNA methylation. Results from this study may lead to improved management recommendations for individuals with advanced IM. Additionally, the resulting biobank of gastric tissue, blood, urine, saliva and stool will enable state-of-the-art molecular assays and serve as a resource for future research in this area by multiple DCEG investigators.