Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer

作者：Tiffany Sia, Anna Maio, Yelena M. Kemel, Kanika S. Arora, Sushmita Gordhandas, Ryan Matthew Kahn, Erin E. Salo‐Mullen, Margaret A. Sheehan, Prince Rainier Tejada, Chaitanya Bandlamudi, Qin C Zhou, Alexia E. Iasonos, Rachel Nicole Grisham, Roisin Eilish O'Cearbhaill, William P. Tew, Kara Long Roche, Oliver Zivanovic, Yukio Sonoda, Ginger J. Gardner, S. Dennis, Alicia J. Latham, Maria Isabel Carlo, Yonina R. Murciano‐Goroff, Marie Will, Michael Francis Walsh, Mark E. Robson, Diana L. Mandelker, Michael F. Berger, Nadeem R. Abu‐Rustum, Carol L. Brown, Kenneth Offit, Jada G. Hamilton, Carol A Aghajanian, Britta Weigelt, Zsofia Kinga Stadler, Ying L. Liu · 发表于：JCO Precision Oncology · 年份：2023 · DOI：10.1200/po.23.00137 · 被引用次数：13 · 研究领域：BRCA gene mutations in cancer、Genomics and Rare Diseases、Genetic Associations and Epidemiology

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.