Pathogenic germline variants among women with uterine cancer by ancestry: A commercial laboratory collaborative research registry study Journal Article

  

Authors:	Johnson, C. R.; Aryasomayajula, C.; Francoeur, A. A.; Stewart, C.; Sia, T. Y.; Darcy, K. M.; Tian, C.; Kapp, D. S.; Liu, Y. L.; Chan, J. K.
Article Title:	Pathogenic germline variants among women with uterine cancer by ancestry: A commercial laboratory collaborative research registry study
Abstract:	Objective: Uterine cancer (UC) is the most common gynecologic cancer in the United States, and 5–15 % of patients harbor a germline pathogenic variant (gPV) in a cancer predisposition gene. This study aims to characterize the germline landscape of patients with UC by self-identified ancestry. Methods: Patients with UC who received germline testing were identified from the publicly available Myriad Collaborative Research Registry. Rates of gPVs were calculated, overall and by self-reported ancestry, with a focus on genes associated with UC, including Lynch syndrome (LS) and homologous recombination-related (HR) genes. Results: Among 35,310 patients with UC, 23,081 (65.4 %) identified as White, 3683 (10.4 %) as Hispanic, 2132 (6.0 %) as Black, 1244 (3.5 %) as Ashkenazi Jewish (AJ), 1093 (3.1 %) as Asian, and 7550 (21.4 %) as Other. Overall, 5141 (14.6 %) patients had a gPV, with highest rates among White (15.5 %) and Asian (17.8 %) compared to Black (10.4 %) and Hispanic (11.6 %) patients, p < 0.0001. LS gPVs were observed in 3155 (8.9 %) patients and was most prevalent in Asian women (12.9 %), particularly MLH1 and MSH2-associated LS. HR-related gPVs were found in 1066 (3.0 %) patients overall and were most common in AJ (4.1 %) and Black (4.0 %) patients, with high rates of BRCA1/2 gPVs in AJ patients and non-BRCA HR-related gPVs in Black patients. Conclusions: Of the over 35,000 patients with UC, 14.5 % had a gPV identified, supporting consideration of universal germline testing in endometrial cancer given high actionability. We observed heterogeneity in gPVs by self-reported ancestry with Black and Hispanic patients having the lowest rates, potentially contributing to disparities in UC. © 2025 Elsevier Inc.
Keywords:	adult; controlled study; aged; major clinical study; endometrium cancer; homologous recombination; cancer susceptibility; uterus cancer; lynch syndrome; uterine cancer; caucasian; hispanic; female genital tract cancer; germline mutation; human; female; article; germline pathogenic variants; homologous recombination variants; self-reported ancestry
Journal Title:	Gynecologic Oncology
Volume:	197
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2025-06-01
Start Page:	83
End Page:	90
Language:	English
DOI:	10.1016/j.ygyno.2025.04.585
PROVIDER:	scopus
PUBMED:	40300426
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105003552556&doi=10.1016%2fj.ygyno.2025.04.585&partnerID=40&md5=39725cb4a939e6151eea4fc1cb7c8a78
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/225443