70岁以上卵巢癌患者胚系基因检测的真实世界数据：指导咨询与风险降低

原文

BACKGROUND: Older women are underrepresented in hereditary cancer guidelines, and the prevalence of pathogenic or likely pathogenic (P/LP) germline variants in ovarian cancer (OC) patients aged ≥70 remains poorly characterized. Current recommendations for risk-reducing interventions and surveillance rely heavily on variant and family history (FH), yet their applicability in older populations is uncertain. We evaluated age-stratified prevalence of P/LP variants at OC diagnosis to identify at-risk older patients and inform more inclusive genetic counseling strategies. METHODS: We conducted a retrospective analysis of 113,236 OC patients undergoing germline testing through the Myriad Collaborative Research Registry (1996-2024). Variant prevalence, ancestry, FH, and testing patterns were evaluated across age groups, with focus on patients ≥70. RESULTS: Overall, 14,513 patients (12.8%) harbored a P/LP variant, including 13,049 (11.5%) in established OC susceptibility genes. Among patients ≥70 (20%, n = 22,593), 6.6% carried variants in established genes compared with 12.8% in those <70 (p < 0.01). BRCA1/2 and Lynch syndrome variants declined with age; BRCA2 exceeded BRCA1 in patients ≥70. Moderate-penetrance variants (BRIP1,PALB2) were relatively enriched, while ATM and RAD51C/D remained stable. PMS2 were more common than previously reported and declined with age (p = 0.03). Patients ≥70 were 1.5-fold less likely to report a cancer FH. CONCLUSION: Despite lower prevalence, a clinically meaningful proportion of patients ≥70 harbor actionable P/LP variants, often without FH that would prompt risk-reducing interventions. These findings suggest reduced sensitivity of FH-based risk assessment in older individuals, supporting age-inclusive genetic counseling and testing strategies extending beyond FH-based criteria.