Universal Germline Genetic Testing after a Diagnosis of Cancer
Menée à partir du séquençage de l'ADN issu d'échantillons sanguins et d'échantillons salivaires prélevés sur 39 184 patients atteints d'une tumeur solide diagnostiquée entre janvier 2015 et 2024 (32 types tumoraux), cette étude examine la corrélation entre la prévalence de variants pathogènes constitutionnels et l'âge au diagnostic puis détermine la pertinence de restreindre les tests de génétique constitutionnelle aux patients âgés de moins de 50 ans
Age at diagnosis among patients with cancer is a predictor of pathogenic germline variant prevalence, yet age thresholds often misclassify genetic risk. We performed germline sequencing of 39,184 unselected patients with solid malignancies spanning 32 tumor types, interrogating >90 cancer predisposition genes independent of clinical suspicion. Patients were stratified into early-, average-, and late-onset groups based on standard deviations from tumor-specific mean age at diagnosis. Pathogenic variant prevalence inversely correlated with age at diagnosis: 18.4% in early-onset tumors, 15.6% in average-onset tumors, and 12.3% in late-onset tumors (P < 0.001). Variants in high/moderate-penetrance genes accounted for the enrichment in early-onset cases (12.4%, early-onset; 8.9%, average-onset; 5.1%, late-onset; P < 0.001). Restricting hereditary cancer testing to patients diagnosed before age 50, as is typically done, would miss 4,601 pathogenic variant carriers, 72% of all variants detected. These findings support broad-based germline testing beyond conventional age-based criteria, reflecting the burden of hereditary risk even among late-onset cases.
Cancer Discovery , résumé, 2026