Background: Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulcerative disease of the oral cavity in the United States. The etiopathogenesis of RAS is unknown. Genetic and environmental risk factors are thought to play a role. Our preliminary analyses of the demographic distribution of RAS indicate that the prevalence of this condition is higher in Mexican-Americans. However, no detailed analyses have been conducted thus far on genetic and environmental risk factors for RAS in this population. Methods: We will conduct a case-control study to collect epidemiologic data through questionnaires and clinical examinations to determine risk factors for RAS in a South Texas population with a large Mexican-American ethnic group (Specific Aim #1). We will conduct a pilot study of gene expression in RAS and control tissue to gather preliminary data on the role of matrix metalloproteinases (MMPs), their inhibitors (i.e., tissue inhibitors of MMPs and somatostatin), and MMP-related cytokines in the pathogenesis of RAS (Specific Aim #2). Lastly, we will bank data and DNA collected through questionnaires, examinations, blood drawing, and gene expression analyses of biopsy tissue to facilitate future genetic epidemiologic studies of RAS (Specific Aim #3). Outcome/Benefit: This is the first study of a series of genetic epidemiologic studies of RAS. The case- control study will provide important information on the role of environmental, socio-economic, and host- related risk factors for RAS. The pilot study will provide new preliminary data on the role of MMPs, their inhibitors, MMP-related cytokines, and other genes in the pathogenesis of RAS. Collectively, the results of this research and the banked data will constitute an important foundation for future epidemiologic studies aimed at understanding the combined role of environmental and genetic risk factors for RAS. Relevance to Public Health: This study is aimed at understanding the cause of painful recurrent mouth ulcers (canker sores), which is unknown. Understanding the cause of canker sores can lead to better treatments for patients affected by this condition. [unreadable] [unreadable] [unreadable]