Synapse - Germline pathogenic variants and genetic counseling by ancestry in patients with epithelial ovarian cancer

Germline pathogenic variants and genetic counseling by ancestry in patients with epithelial ovarian cancer Journal Article

Authors:	Sia, T. Y.; Maio, A.; Kemel, Y. M.; Arora, K. S.; Gordhandas, S. B.; Kahn, R. M.; Salo-Mullen, E. E.; Sheehan, M. A.; Tejada, P. R.; Bandlamudi, C.; Zhou, Q.; Iasonos, A.; Grisham, R. N.; O'Cearbhaill, R. E.; Tew, W. P.; Long Roche, K.; Zivanovic, O.; Sonoda, Y.; Gardner, G. J.; Chi, D. S.; Latham, A. J.; Carlo, M. I.; Murciano-Goroff, Y. R.; Will, M.; Walsh, M. F.; Robson, M. E.; Mandelker, D. L.; Berger, M. F.; Abu-Rustum, N. R.; Brown, C. L.; Offit, K.; Hamilton, J. G.; Aghajanian, C.; Weigelt, B.; Stadler, Z. K.; Liu, Y. L.
Article Title:	Germline pathogenic variants and genetic counseling by ancestry in patients with epithelial ovarian cancer
Abstract:	PURPOSE To evaluate rates of germline pathogenic/likely pathogenic variants (PVs) and genetic counseling by ancestry in patients with epithelial ovarian cancer (EOC). METHODS Patients with pathologically confirmed EOC who underwent clinical tumor-normal sequencing from January 1, 2015, to December 31, 2020, inclusive of germline analysis of >= 76 genes were included. Patients with newly identified PVs were referred for Clinical Genetics Service (CGS) counseling. Ancestry groups were defined using self-reported race/ethnicity and Ashkenazi Jewish (AJ) heritage. Genetic ancestry was inferred computationally using validated algorithms. Logistic regression models were built. RESULTS Of 1,266 patients, self-reported ancestry (AJ, 17%; Asian, 10%; Black/African American, 5.4%; Hispanic, 6.2%; non-Hispanic White, 57%; other, 0.16%; unknown, 4.0%) correlated with genetic ancestry (AJ ancestry, 18%; admixed, 10%; African, 4%; East Asian [EAS], 6%; European, 56%; Native American, 0.2%; South Asian [SAS], 4%; unknown, 2%). Germline PVs were observed in 313 (25%) patients, including 195 (15%) with PVs in EOC-associated genes. Those with PVs were younger at diagnosis (59 v 62 years; P < .001) and more likely to have high-grade serous ovarian cancer (83% v 72%; P = .009). PV prevalence varied between ancestry groups (P < .001), with highest rates in the AJ (39.9%) and Asian (26.5%) groups and similar rates (>10%) across other ancestry groups. Use of genetic ancestry demonstrated similar findings and further characterized high rates of PV in EAS/SAS groups. Younger age, high-grade serous histology, and self-reported AJ or Asian ancestry were associated with PV in an EOC-associated gene. Rates of CGS counseling for newly identified PVs were high (80%) across ancestry groups. CONCLUSION Rates of PV, particularly in EOC-associated genes, were high regardless of ancestry, with similar rates of counseling between groups, emphasizing the importance of universal genetic testing in all patients with EOC.
Keywords:	prevalence; risk; tumor; breast-cancer; women; guideline; brca2 mutations; fallopian-tube; american-college; medical genetics
Journal Title:	JCO Precision Oncology
Volume:	7
ISSN:	2473-4284
Publisher:	American Society of Clinical Oncology
Date Published:	2023-09-01
Start Page:	e2300137
Language:	English
ACCESSION:	WOS:001197689200039
DOI:	10.1200/po.23.00137
PROVIDER:	wos
PMCID:	PMC10861001
PUBMED:	37738546
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Ying L. Liu -- Author Margaret Sheehan's name is listed with a different middle initial on the original publication -- Source: Wos