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

Tiffany Y Sia; Anna Maio; Yelena M Kemel; Kanika S Arora; Sushmita B Gordhandas; Ryan M Kahn; Erin E 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; Dennis S Chi; Alicia J Latham; Maria I Carlo; Yonina R Murciano-Goroff; Marie Will; Michael F Walsh; Mark E Robson; Diana L 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

doi:10.1200/PO.23.00137

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

Tiffany Y Sia, Anna Maio, Yelena M Kemel, Kanika S Arora, Sushmita B Gordhandas, Ryan M Kahn, Erin E 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, Dennis S ChiAlicia J Latham, Maria I Carlo, Yonina R Murciano-Goroff, Marie Will, Michael F Walsh, Mark E Robson, Diana L 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	e2300137
Journal	JCO precision oncology
Volume	7
DOIs	https://doi.org/10.1200/PO.23.00137
State	Published - Sep 2023
Externally published	Yes

Keywords

Female
Humans
Genetic Counseling
Carcinoma, Ovarian Epithelial/genetics
Genetic Testing
Germ Cells
Ovarian Neoplasms/genetics

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10.1200/PO.23.00137

Cite this

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., ... Liu, Y. L. (2023). Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer. JCO precision oncology, 7, e2300137. https://doi.org/10.1200/PO.23.00137

Sia, TY, Maio, A, Kemel, YM, Arora, KS, Gordhandas, SB, Kahn, RM, Salo-Mullen, EE, Sheehan, MA, Tejada, PR, Bandlamudi, C, Zhou, Q, Iasonos, A, Grisham, RN, O'Cearbhaill, RE, Tew, WP, Long Roche, K, Zivanovic, O, Sonoda, Y, Gardner, GJ, Chi, DS, Latham, AJ, Carlo, MI, Murciano-Goroff, YR, Will, M, Walsh, MF, Robson, ME, Mandelker, DL, Berger, MF, Abu-Rustum, NR, Brown, CL, Offit, K, Hamilton, JG, Aghajanian, C, Weigelt, B, Stadler, ZK & Liu, YL 2023, 'Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer', JCO precision oncology, vol. 7, pp. e2300137. https://doi.org/10.1200/PO.23.00137

@article{3b632ac923e2463bbae54084eb9e446d,

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 = "Female, Humans, Genetic Counseling, Carcinoma, Ovarian Epithelial/genetics, Genetic Testing, Germ Cells, Ovarian Neoplasms/genetics",

author = "Sia, \{Tiffany Y\} and Anna Maio and Kemel, \{Yelena M\} and Arora, \{Kanika S\} and Gordhandas, \{Sushmita B\} and Kahn, \{Ryan M\} and Salo-Mullen, \{Erin E\} and Sheehan, \{Margaret A\} and Tejada, \{Prince Rainier\} and Chaitanya Bandlamudi and Qin Zhou and Alexia Iasonos and Grisham, \{Rachel N\} and O'Cearbhaill, \{Roisin E\} and Tew, \{William P\} and \{Long Roche\}, Kara and Oliver Zivanovic and Yukio Sonoda and Gardner, \{Ginger J\} and Chi, \{Dennis S\} and Latham, \{Alicia J\} and Carlo, \{Maria I\} and Murciano-Goroff, \{Yonina R\} and Marie Will and Walsh, \{Michael F\} and Robson, \{Mark E\} and Mandelker, \{Diana L\} and Berger, \{Michael F\} and Abu-Rustum, \{Nadeem R\} and Brown, \{Carol L\} and Kenneth Offit and Hamilton, \{Jada G\} and Carol Aghajanian and Britta Weigelt and Stadler, \{Zsofia K\} and Liu, \{Ying L\}",

year = "2023",

month = sep,

doi = "10.1200/PO.23.00137",

language = "English",

volume = "7",

pages = "e2300137",

journal = "JCO precision oncology",

issn = "2473-4284",

}

TY - JOUR

T1 - Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer

AU - Sia, Tiffany Y

AU - Maio, Anna

AU - Kemel, Yelena M

AU - Arora, Kanika S

AU - Gordhandas, Sushmita B

AU - Kahn, Ryan M

AU - Salo-Mullen, Erin E

AU - Sheehan, Margaret A

AU - Tejada, Prince Rainier

AU - Bandlamudi, Chaitanya

AU - Zhou, Qin

AU - Iasonos, Alexia

AU - Grisham, Rachel N

AU - O'Cearbhaill, Roisin E

AU - Tew, William P

AU - Long Roche, Kara

AU - Zivanovic, Oliver

AU - Sonoda, Yukio

AU - Gardner, Ginger J

AU - Chi, Dennis S

AU - Latham, Alicia J

AU - Carlo, Maria I

AU - Murciano-Goroff, Yonina R

AU - Will, Marie

AU - Walsh, Michael F

AU - Robson, Mark E

AU - Mandelker, Diana L

AU - Berger, Michael F

AU - Abu-Rustum, Nadeem R

AU - Brown, Carol L

AU - Offit, Kenneth

AU - Hamilton, Jada G

AU - Aghajanian, Carol

AU - Weigelt, Britta

AU - Stadler, Zsofia K

AU - Liu, Ying L

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

KW - Female

KW - Humans

KW - Genetic Counseling

KW - Carcinoma, Ovarian Epithelial/genetics

KW - Genetic Testing

KW - Germ Cells

KW - Ovarian Neoplasms/genetics

U2 - 10.1200/PO.23.00137

DO - 10.1200/PO.23.00137

M3 - Article

C2 - 37738546

SN - 2473-4284

VL - 7

SP - e2300137

JO - JCO precision oncology

JF - JCO precision oncology

ER -