Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer
Tiffany Sia, Anna Maio, Yelena Kemel, Kanika Arora, Sushmita Gordhandas, Ryan Kahn, Erin Salo‐Mullen, Margaret A. Sheehan, Prince Rainier Tejada, Chaitanya Bandlamudi, Qin Zhou, Alexia Iasonos, Rachel N. Grisham, Roisin E. O’Cearbhaill, William P. Tew, Kara Long Roche, Oliver Zivanovic, Yukio Sonoda, Ginger J. Gardner, S. Dennis, Alicia Latham, Maria I. Carlo, Yonina R. Murciano‐Goroff, Marie Will, Michael F. Walsh, Mark E. Robson, Diana Mandelker, Michael F. Berger, Nadeem R. Abu‐Rustum, Carol L. Brown, Kenneth Offit, Jada G. Hamilton, Carol Aghajanian, Britta Weigelt, Zsofia K. Stadler, Ying L. Liu
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: < .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.