Early onset gastric cancer: clinical and molecular insights into a rising epidemic among younger adults.

Abstract

Background: Early onset gastric cancer (EOGC), defined as gastric cancer occurring in individuals aged 49 years or younger, presents distinct clinical and molecular characteristics compared to late-onset gastric cancer (LOGC). Despite the increasing incidence of EOGC, limited data exist regarding its demographic, risk factor, and molecular profiles. This study aimed to compare the clinicopathologic and molecular features of EOGC and LOGC and characterize the demographic, clinical, and molecular characteristics of EOGC in a diverse cohort to elucidate potential risk factors and disease behavior.

Methods: A retrospective cohort study was conducted on 437 gastric carcinoma patients screened at Baylor Scott & White Health (2002-2022). Demographic, clinical, and molecular data, including Helicobacter pylori infection, lifestyle factors, histopathology, and biomarkers (HER2, MSI), were analyzed.

Results: Of the 437 gastric carcinoma cases screened, 32 patients had EOGC, while 51 had LOGC with available clinical and molecular data. EOGC was associated with a higher proportion of females (P = 0.001) and greater racial/ethnic diversity, including a higher prevalence of Hispanic (41% vs 13.7%) and African American patients (34.3% vs 13.7%). Modifiable risk factor analysis revealed a significant association between EOGC and H. pylori infection (P = 0.001), whereas alcohol use was more common in LOGC (P = 0.041). EOGC was more frequently diagnosed at advanced stages (P = 0.02) and exhibited a higher prevalence of signet ring cell carcinoma (P = 0.003) and poorly differentiated tumors (P < 0.001). Molecular analysis showed low HER2 positivity (4.2%) and mismatch repair deficiency (8.3%) in EOGC, suggesting distinct molecular features. The overall 5-year survival rate for EOGC was 22.6%, significantly lower in patients diagnosed at advanced stages (III/IV 5.9% vs I/II 63.6%, P = 0.028).

Conclusion: This study underscores the aggressive nature of EOGC, highlighting its advanced-stage presentation, poor survival, and distinct molecular pathways. The high prevalence of H. pylori infection, obesity, and smoking reinforces the need for targeted prevention strategies. Given its rising incidence and late-stage diagnosis, risk-based screening, optimized treatment protocols, and novel therapeutic strategies are crucial for improving patient outcomes.