Abstract 2274: Identification of predisposition and progression gastric cancer biomarkers in Latinos

Abstract

Gastric cancer (GC) disproportionally affects people of Latino ancestry and represent a leading cause of incidence and mortality disparities in this minority populations. When compared to Non-Latino Whites, Latinos are ~2-fold more likely to be diagnosed with and to die of GC. The goal of our research program is to contribute to GC research in patients of Latino ancestry and advance cancer health disparity research. One of the research projects aims at identifying germline variants associated with GC risk. To do so, we are identifying novel gastric cancer genes and detecting mutations in previously reported GC genes, using whole-exome sequencing, in 500 patients who have been diagnosed with early-onset GC and/or who had GC and family history of cancer. Whole exome sequence data collection was recently completed and is being analyzed with the primary goals of estimating the prevalence and penetrance in known cancer genes as well as the identification of new GC genes. Using in-house exome data and publicly available genetic data, we will identify variants with predicted impact in the phenotype to design a panel that will be used for their detection in gastric preneoplasia biopsies. These variants will be tested using duplex sequencing, a highly sensitive method that can detect very rare mutations with ultra-depth sequencing. We will then select the variants with likely functional consequences for tumor initiation and/or progression to generate isogenic gastric organoids to investigate their effect in proliferation, differentiation, and gene expression. We aim to generate a body of work that can be used for risk assessment, prevention, early diagnostic, and that will lead to better outcomes for GC in this important U.S. minority. Dr. Ana Estrada-Florez is the recipient of the AACR Cancer Health Disparities Fellowship. Citation Format: Ana Patricia Estrada-Florez, Paul Lott, Ted Toal, Nicole Halmai, Elizabeth Quino, Alma Poceros-Coba, Alix Guevara, Fabian Castro, Jhon Suarez, John Mcpherson, Rasika Venkatesh, Hongyong Zhang, Apri Vang, Guadalupe Polanco, Joana Guerra, Graciela Molina, Carol Parra, Adriana Della Valle, Esteban Castelao, Manuel Teixeira, Mabel Bohorquez, Javier Torres, Alejandro Carvajal Corvalan, Luis G. Carvajal-Carmona. Identification of predisposition and progression gastric cancer biomarkers in Latinos [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2274.