Molecular features of early- vs. late-onset gastric cancer: a systematic review and meta-analysis

Early-onset gastric cancer (EOGC), diagnosed before age 50, is characterized by distinct clinicopathological features, though its molecular landscape remains poorly defined.

A systematic literature search of PubMed, Embase, and Web of Science identified studies comparing molecular characteristics of EOGC and late-onset gastric cancer (LOGC). Meta-analyses assessed differences in The Cancer Genome Atlas (TCGA) molecular subtypes, gene mutations, therapeutic biomarkers, and serum tumor markers. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated; heterogeneity was assessed using the I² statistic.

EOGC was associated with a higher prevalence of the genomically stable (GS) subtype (OR = 1.71, 95% CI: 1.37-2.12) and a lower prevalence of the chromosomal instability (CIN) subtype (OR = 0.62, 95% CI: 0.50-0.77). CDH1 mutations were more frequent in EOGC (OR = 3.44, 95% CI: 2.85-4.16), while HER2 expression (OR = 0.54, 95% CI: 0.43-0.67), dMMR/MSI-H status (OR = 0.25, 95% CI: 0.12-0.53), and p53 expression (OR = 0.56, 95% CI: 0.39-0.82) were significantly lower. Serum markers including CEA and CA19-9 were also less frequently elevated in EOGC.

EOGC represents a biologically distinct subset of gastric cancer with unique genomic and immunological features. These findings support age-specific diagnostic approaches and emphasize the value of multiomic strategies to uncover the mechanisms driving early-onset disease.