Background: Overall the incidence of gastric cancer is declining in the United States; however, the incidence of early-onset gastric cancer is increasing. We sought to elucidate clinical and genomic characteristics and risk factors for early-onset gastric cancer compared with late-onset gastric cancer. Methods: We utilized the Surveillance, Epidemiology, and End Results database (1973–2015), the Behavioral Risk Factor Surveillance Survey, and The Cancer Genome Atlas to characterize early-onset gastric cancer. Results: The incidence of early-onset gastric cancer increased during the study period and now comprises >30% of all gastric cancer in the United States. Early-onset gastric cancer was associated with higher grade (55.2 vs 46.9%), signet-ring cells (19.0 vs 10.4%), diffuse histology (25.7 vs 15.0%), and metastatic disease (49.5 vs 40.9%, all P < .01) compared with late-onset gastric cancer. Early-onset gastric cancer was more likely to be Epstein-Barr virus (7.7 vs 5.1%) or genomically stable (22.5 vs 8.1%) subtype, whereas late-onset gastric cancer was more likely to be microsatellite instability subtype (18.6 vs 5.6%; all P < .01). Risk factors for gastric cancer were less correlated with early-onset gastric cancer compared with late-onset gastric cancer. Conclusion: The incidence of early-onset gastric cancer has been steadily increasing in the United States, comprising >30% of new gastric cancer cases today. Early-onset gastric cancer is genetically and clinically distinct from traditional gastric cancer. Additional investigations are warranted to better understand this alarming phenomenon.
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