Molecular characteristics and clinical outcomes of patients with gastroesophageal cancer diagnosed at ages younger than 50 years.

Differential somatic and germline molecular profile of early-onset gastroesophageal cancers — germline CDH1 enriched in patients <50 years

Among 5,863 gastroesophageal cancer patients in the Tempus clinicogenomic database, 785 diagnosed before age 50 exhibited a distinct germline profile with significantly higher incidence of CDH1 (2.2% vs. 0.3%, q=0.001) and TP53 (0.6% vs. 0%, q=0.039) germline variants compared with older patients. Early-onset cases also showed a distinct somatic molecular profile: lower TMB-H, lower MSI-H, higher somatic CDH1 mutations, and longer median metastatic survival (11 vs. 8.5 months). These findings suggest distinct etiological mechanisms and germline genetic counseling implications for young gastroesophageal cancer patients.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This article supports systematic referral to cancer genetics for gastroesophageal cancer diagnosed before age 50: a 2.2% germline CDH1 pathogenic variant rate is clinically significant, with direct implications for relatives (gastric surveillance, prophylactic gastrectomy). The concurrent enrichment in somatic CDH1 mutations suggests distinct tumorigenesis mechanisms between younger and older populations.

Clinical impact : 2/3 · Evidence strength : 2/3 · Novelty : 2/2 · Sample size : 1/1 · Journal quality : 1/1 → Total : 8/10