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PMID: 42114202 已发表 · ppublish 英语

Real-world genetic testing data of ovarian cancer patients: Informing counseling and risk reduction in patients over age seventy.

Gynecologic oncology ·第 209 卷 ·2026-06-00

Shachar E, Rotkop G, Haas R, Frankenthal R, Kamara D, Demirjian M, Kwan L, Cummings S, Roscow B, Salani R, Spellman PT, Karlan B, Chase DM

摘要

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. 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. 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. 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.

关键词
BRCA Elderly Hereditary cancer Lynch syndrome Ovarian cancer Prevention Risk reduction
文献信息
期刊
Gynecologic oncology
期刊简称
Gynecol Oncol
ISSN
1095-6859
发表日期
2026-06-00
语言
英语
国家/地区
United States
NLM ID
0365304
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