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

被引：5

作者：

Sia, Tiffany Y. ^{[1
]}

Maio, Anna ^{[2
]}

Kemel, Yelena M. ^{[3
]}

Arora, Kanika S. ^{[4
]}

Gordhandas, Sushmita B. ^{[1
]}

Kahn, Ryan M. ^{[1
]}

Salo-Mullen, Erin E. ^{[2
]}

Sheehan, Margaret A. ^{[2
]}

Tejada, Prince Rainier ^{[2
]}

Bandlamudi, Chaitanya ^{[4
]}

Zhou, Qin ^{[5
]}

Iasonos, Alexia ^{[5
]}

Grisham, Rachel N. ^{[6
,7
]}

O'Cearbhaill, Roisin E. ^{[6
,7
]}

Tew, William P. ^{[6
,7
]}

Roche, Kara Long ^{[1
,8
]}

Zivanovic, Oliver ^{[1
,8
]}

Sonoda, Yukio ^{[1
,8
]}

Gardner, Ginger J. ^{[1
,8
]}

Chi, Dennis S. ^{[1
,8
]}

Latham, Alicia J. ^{[2
,7
]}

Carlo, Maria I. ^{[2
,7
]}

Murciano-Goroff, Yonina R. ^{[2
,7
]}

Will, Marie ^{[2
,7
]}

Walsh, Michael F. ^{[2
,7
]}

Robson, Mark E. ^{[2
,7
]}

Mandelker, Diana L. ^{[4
]}

Berger, Michael F. ^{[4
]}

Abu-Rustum, Nadeem R. ^{[1
,8
]}

Brown, Carol L. ^{[1
,8
]}

Offit, Kenneth ^{[2
,7
]}

Hamilton, Jada G. ^{[2
,9
,10
]}

Aghajanian, Carol ^{[6
,7
]}

Weigelt, Britta ^{[4
]}

Stadler, Zsofia K. ^{[2
,7
]}

Liu, Ying L. ^{[2
,6
,7
,11
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY USA

[3] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, New York, NY USA

[4] Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA

[5] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA

[6] Mem Sloan Kettering Canc Ctr, Dept Med, Gynecol Med Oncol Serv, New York, NY USA

[7] Weill Cornell Med Coll, Dept Med, New York, NY USA

[8] Weill Cornell Med Coll, Dept Obstet & Gynecol, New York, NY USA

[9] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA

[10] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY USA

[11] Mem Sloan Kettering Canc Ctr, Lead Inherited Gynecol Canc Program, Clin Genet Serv, Gynecol Med Oncol, 300 East 66th St,1309, New York, NY 10065 USA

来源：

JCO PRECISION ONCOLOGY | 2023年 / 7卷

基金：

美国国家卫生研究院;

关键词：

BRCA2; MUTATIONS; MEDICAL GENETICS; AMERICAN-COLLEGE; FALLOPIAN-TUBE; BREAST-CANCER; WOMEN; TUMOR; RISK; PREVALENCE; GUIDELINE;

D O I：

10.1200/PO.23.00137

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

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