Bergquist JR, et al. - Early-onset gastric cancer was compared with late-onset gastric cancer regarding clinical and genomic characteristics and risk factors via utilizing the Surveillance, Epidemiology, and End Results database (1973–2015), the Behavioral Risk Factor Surveillance Survey, and The Cancer Genome Atlas. During the study period, an increase in the incidence of early-onset gastric cancer was observed and now this comprises >30% of all gastric cancer in the United States. Relative to late-onset gastric cancer, early-onset gastric cancer was associated with higher grade, signet-ring cells, diffuse histology, and metastatic disease. Early-onset gastric cancer was more likely to be Epstein-Barr virus or genomically stable subtype, whereas late-onset gastric cancer was more likely to be microsatellite instability subtype. Early-onset gastric cancer vs late-onset gastric cancer was less correlated to risk factors for gastric cancer. These findings suggest genetically and clinically distinct nature of early-onset gastric cancer from traditional gastric cancer.