Clinical and Genomic Characteristics of Mexican Patients with Early Onset Gastric Adenocarcinoma

Gastric cancer is a leading cause of cancer-related deaths in Mexico, with a rising incidence of early onset gastric cancer (EOGC) in young adults. This single-center study aimed to describe the clinical and mutational characteristics associated with EOGC in Mexican patients, based on an age cutoff of 50 years.

Clinical information was retrieved from electronic records and compared between EOGC and late-onset gastric cancer (LOGC). Whole exome sequencing data from 50 patients were analyzed and compared between both groups to elucidate the genomic overview of EOGC.

Clinical data from 2,034 patients were analyzed. Of those, 35.69% had EOGC, with higher proportions of women (52.50%), diffuse histology (74.38%), signet ring cells (79.90%), and advanced stages (IVB: 79.58%; all p <0.001). Multivariate analysis in young patients identified ECOG (hazard ratio [HR]: 1.49) and clinical stage (HR: 1.78) as independent prognostic factors that increased mortality risk. However, the presence of Helicobacter pylori (HR: 0.76) and participation in genetic counseling (HR: 0.61) were independent prognostic factors that decreased the mortality risk. The molecular profile of Mexican patients demonstrated a high prevalence of CDH1 mutations and SBS44 mutational signatures.

Mexican patients demonstrated higher rates of EOGC compared to other ethnicities. Genetic counseling enhances the overall survival of patients with EOGC; efforts should be made to incorporate it into routine practice. Molecular profiling revealed high CDH1 and SBS44 prevalence; however, sample size limitations warrant caution.