Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer

Elisa M. Ledet; Earle F. Burgess; Alexandra O. Sokolova; Ellen B. Jaeger; Whitley Hatton; Marcus Moses; Patrick Miller; Patrick Cotogno; Jodi Layton; Pedro Barata; Brian E. Lewis; Mari Nakazawa; Jason Zhu; Beth Dellinger; Sara Elrefai; Nellie N. Nafissi; Jan B. Egan; Neal Shore; Rana R. McKay; Alan H. Bryce; Heather H. Cheng; Emmanuel S. Antonarakis; Oliver Sartor

doi:10.1002/pros.24123

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer

Elisa M. Ledet, Earle F. Burgess, Alexandra O. Sokolova, Ellen B. Jaeger, Whitley Hatton, Marcus Moses, Patrick Miller, Patrick Cotogno, Jodi Layton, Pedro Barata, Brian E. Lewis, Mari Nakazawa, Jason Zhu, Beth Dellinger, Sara Elrefai, Nellie N. Nafissi, Jan B. Egan, Neal Shore, Rana R. McKay, Alan H. BryceHeather H. Cheng, Emmanuel S. Antonarakis, Oliver Sartor

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

29 Scopus citations

Abstract

BACKGROUND: The goal of this study is to evaluate germline genetic variants in African American men with metastatic prostate cancer as compared to those in Caucasian men with metastatic prostate cancer in an effort to understand the role of genetic factors in these populations.

METHODS: African American and Caucasian men with metastatic prostate cancer who had germline testing using multigene panels were used to generate comparisons. Germline genetic results, clinical parameters, and family histories between the two populations were analyzed.

RESULTS: A total of 867 patients were included in this retrospective study, including 188 African American and 669 Caucasian patients. There was no significant difference in the likelihood of a pathogenic or likely-pathogenic variants (PV/LPVs) between African American and Caucasian patients (p = .09). African American patients were more likely to have a variant of unknown significance than Caucasians (odds ratio [OR] = 1.95; p < .0001). BRCA1 PV/LPVs were higher in African Americans (OR = 4.86; p = .04). African American patients were less likely to have a PV/LPV in non-BRCA DNA repair genes (OR = 0.30; p = .008). Family history of breast (OR = 2.09; p = .002) or ovarian cancer (OR = 2.33; p = .04) predicted PV/LPVs in Caucasians but not African-Americans. This underscores the limitations of family history in AA men and the importance of personal history to guide germline testing in AA men.

CONCLUSIONS: In metastatic prostate cancer patients, PV/LPVs of tested genes did not vary by race, BRCA1 PV/LPVs were more common in the African American subset. However, PV/LPVs in non-BRCA DNA repair genes were less likely to be encountered in African Americans. Family history associated with genetic testing results in Caucasians only.

Original language	English (US)
Pages (from-to)	433-439
Number of pages	7
Journal	Prostate
Volume	81
Issue number	7
DOIs	https://doi.org/10.1002/pros.24123
State	Published - Apr 2021
Externally published	Yes

Bibliographical note

Funding Information:
Dr. Sartor has research funding to his institution from AAA, AstraZeneca, Bayer, Merck, Endocyte, Progenics, Novartis, and Janssen. Dr. Sartor has received consulting fees from Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Dendreon, Bristol-Myers Squibb, Invitae, Merck, Innocrin, Sotio, AAA, AstraZeneca, Bayer, Endocyte, Progenics, Novartis, Janssen, Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Noria Therapeutics, Clovis, Myriad, Noxopharm, Point Biopharm, Tenebio, Theragnostics, Telix, Clarity Pharmaceuticals, and Fusion. Dr. Shore has research support and consulting fees for AbbVie, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Dendreon, Exact Sciences, Fergene, Foundation Medicine, Invitae, Janssen, Merck, Myriad, Pfizer, and Sanofi, Tolmar. Dr. Cheng receives funding from PNW SPORE CA097186, DOD W81XWH-17-2-0043, NIH CA015704, Prostate Cancer Foundation; research funding to her institution from Clovis, Janssen, Sanofi, Medivation/Astellas, Color Foundation, and consulting fees from AstraZeneca. Dr. Antonarakis has served as a paid consultant/advisor for Invitae, Janssen, Pfizer, Sanofi, Dendreon, Merck, Bristol-Myers Squibb, AstraZeneca, Clovis, Bayer, Constellation, Eli Lilly and Amgen; and has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Bayer, Merck, Bristol-Myers Squibb, AstraZeneca, ESSA and Constellation. Additionally, Dr. Antonarakis is partially supported by the Patrick Walsh Prostate Cancer Research Fund, the Prostate Cancer Foundation, the NCI Cancer Center Support Grant 5P30 CA006973-52, the NIH grant R01 CA238384, and the DOD Clinical Consortium award W81XWH-16-PCRP-CCRSA. Dr. Bryce received honoraria from Foundation Medicine, Novartis, Astellas, and Merck. Dr. McKay has served as a paid consultant for Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Vividion Therapeutics, Bayer and has research funding to her institution from Pfizer and Bayer. Dr. Burgess has received consulting fees from Johnson and Johnson, honoraria from Exelixis and Bayer, and research funding to his institution from Pfizer and Astellas Pharma. Dr. Zhu has served as a paid consultant for NGM Biopharmaceuticals and Bayer. All other authors have no conflict of interests to disclose.

Funding Information:
Dr. Sartor has research funding to his institution from AAA, AstraZeneca, Bayer, Merck, Endocyte, Progenics, Novartis, and Janssen. Dr. Sartor has received consulting fees from Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Dendreon, Bristol‐Myers Squibb, Invitae, Merck, Innocrin, Sotio, AAA, AstraZeneca, Bayer, Endocyte, Progenics, Novartis, Janssen, Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Noria Therapeutics, Clovis, Myriad, Noxopharm, Point Biopharm, Tenebio, Theragnostics, Telix, Clarity Pharmaceuticals, and Fusion. Dr. Shore has research support and consulting fees for AbbVie, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Dendreon, Exact Sciences, Fergene, Foundation Medicine, Invitae, Janssen, Merck, Myriad, Pfizer, and Sanofi, Tolmar. Dr. Cheng receives funding from PNW SPORE CA097186, DOD W81XWH‐17‐2‐0043, NIH CA015704, Prostate Cancer Foundation; research funding to her institution from Clovis, Janssen, Sanofi, Medivation/Astellas, Color Foundation, and consulting fees from AstraZeneca. Dr. Antonarakis has served as a paid consultant/advisor for Invitae, Janssen, Pfizer, Sanofi, Dendreon, Merck, Bristol‐Myers Squibb, AstraZeneca, Clovis, Bayer, Constellation, Eli Lilly and Amgen; and has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Bayer, Merck, Bristol‐Myers Squibb, AstraZeneca, ESSA and Constellation. Additionally, Dr. Antonarakis is partially supported by the Patrick Walsh Prostate Cancer Research Fund, the Prostate Cancer Foundation, the NCI Cancer Center Support Grant 5P30 CA006973‐52, the NIH grant R01 CA238384, and the DOD Clinical Consortium award W81XWH‐16‐PCRP‐CCRSA. Dr. Bryce received honoraria from Foundation Medicine, Novartis, Astellas, and Merck. Dr. McKay has served as a paid consultant for Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol‐Myers Squibb, Astellas Medivation, Dendreon, Vividion Therapeutics, Bayer and has research funding to her institution from Pfizer and Bayer. Dr. Burgess has received consulting fees from Johnson and Johnson, honoraria from Exelixis and Bayer, and research funding to his institution from Pfizer and Astellas Pharma. Dr. Zhu has served as a paid consultant for NGM Biopharmaceuticals and Bayer. All other authors have no conflict of interests to disclose.

Publisher Copyright:
© 2021 The Authors. The Prostate Published by Wiley Periodicals LLC

Keywords

African American
genetics
germline
metastatic prostate cancer
pathogenic variants
racial disparity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/pros.24123

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Ledet, E. M., Burgess, E. F., Sokolova, A. O., Jaeger, E. B., Hatton, W., Moses, M., Miller, P., Cotogno, P., Layton, J., Barata, P., Lewis, B. E., Nakazawa, M., Zhu, J., Dellinger, B., Elrefai, S., Nafissi, N. N., Egan, J. B., Shore, N., McKay, R. R., ... Sartor, O. (2021). Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer. Prostate, 81(7), 433-439. https://doi.org/10.1002/pros.24123

Ledet, EM, Burgess, EF, Sokolova, AO, Jaeger, EB, Hatton, W, Moses, M, Miller, P, Cotogno, P, Layton, J, Barata, P, Lewis, BE, Nakazawa, M, Zhu, J, Dellinger, B, Elrefai, S, Nafissi, NN, Egan, JB, Shore, N, McKay, RR, Bryce, AH, Cheng, HH, Antonarakis, ES & Sartor, O 2021, 'Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer', Prostate, vol. 81, no. 7, pp. 433-439. https://doi.org/10.1002/pros.24123

@article{18de36bc8db344f9a31df24d43b37b3d,

title = "Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer",

abstract = "BACKGROUND: The goal of this study is to evaluate germline genetic variants in African American men with metastatic prostate cancer as compared to those in Caucasian men with metastatic prostate cancer in an effort to understand the role of genetic factors in these populations.METHODS: African American and Caucasian men with metastatic prostate cancer who had germline testing using multigene panels were used to generate comparisons. Germline genetic results, clinical parameters, and family histories between the two populations were analyzed.RESULTS: A total of 867 patients were included in this retrospective study, including 188 African American and 669 Caucasian patients. There was no significant difference in the likelihood of a pathogenic or likely-pathogenic variants (PV/LPVs) between African American and Caucasian patients (p = .09). African American patients were more likely to have a variant of unknown significance than Caucasians (odds ratio [OR] = 1.95; p < .0001). BRCA1 PV/LPVs were higher in African Americans (OR = 4.86; p = .04). African American patients were less likely to have a PV/LPV in non-BRCA DNA repair genes (OR = 0.30; p = .008). Family history of breast (OR = 2.09; p = .002) or ovarian cancer (OR = 2.33; p = .04) predicted PV/LPVs in Caucasians but not African-Americans. This underscores the limitations of family history in AA men and the importance of personal history to guide germline testing in AA men.CONCLUSIONS: In metastatic prostate cancer patients, PV/LPVs of tested genes did not vary by race, BRCA1 PV/LPVs were more common in the African American subset. However, PV/LPVs in non-BRCA DNA repair genes were less likely to be encountered in African Americans. Family history associated with genetic testing results in Caucasians only.",

keywords = "African American, genetics, germline, metastatic prostate cancer, pathogenic variants, racial disparity",

author = "Ledet, {Elisa M.} and Burgess, {Earle F.} and Sokolova, {Alexandra O.} and Jaeger, {Ellen B.} and Whitley Hatton and Marcus Moses and Patrick Miller and Patrick Cotogno and Jodi Layton and Pedro Barata and Lewis, {Brian E.} and Mari Nakazawa and Jason Zhu and Beth Dellinger and Sara Elrefai and Nafissi, {Nellie N.} and Egan, {Jan B.} and Neal Shore and McKay, {Rana R.} and Bryce, {Alan H.} and Cheng, {Heather H.} and Antonarakis, {Emmanuel S.} and Oliver Sartor",

note = "Funding Information: Dr. Sartor has research funding to his institution from AAA, AstraZeneca, Bayer, Merck, Endocyte, Progenics, Novartis, and Janssen. Dr. Sartor has received consulting fees from Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Dendreon, Bristol-Myers Squibb, Invitae, Merck, Innocrin, Sotio, AAA, AstraZeneca, Bayer, Endocyte, Progenics, Novartis, Janssen, Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Noria Therapeutics, Clovis, Myriad, Noxopharm, Point Biopharm, Tenebio, Theragnostics, Telix, Clarity Pharmaceuticals, and Fusion. Dr. Shore has research support and consulting fees for AbbVie, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Dendreon, Exact Sciences, Fergene, Foundation Medicine, Invitae, Janssen, Merck, Myriad, Pfizer, and Sanofi, Tolmar. Dr. Cheng receives funding from PNW SPORE CA097186, DOD W81XWH-17-2-0043, NIH CA015704, Prostate Cancer Foundation; research funding to her institution from Clovis, Janssen, Sanofi, Medivation/Astellas, Color Foundation, and consulting fees from AstraZeneca. Dr. Antonarakis has served as a paid consultant/advisor for Invitae, Janssen, Pfizer, Sanofi, Dendreon, Merck, Bristol-Myers Squibb, AstraZeneca, Clovis, Bayer, Constellation, Eli Lilly and Amgen; and has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Bayer, Merck, Bristol-Myers Squibb, AstraZeneca, ESSA and Constellation. Additionally, Dr. Antonarakis is partially supported by the Patrick Walsh Prostate Cancer Research Fund, the Prostate Cancer Foundation, the NCI Cancer Center Support Grant 5P30 CA006973-52, the NIH grant R01 CA238384, and the DOD Clinical Consortium award W81XWH-16-PCRP-CCRSA. Dr. Bryce received honoraria from Foundation Medicine, Novartis, Astellas, and Merck. Dr. McKay has served as a paid consultant for Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Vividion Therapeutics, Bayer and has research funding to her institution from Pfizer and Bayer. Dr. Burgess has received consulting fees from Johnson and Johnson, honoraria from Exelixis and Bayer, and research funding to his institution from Pfizer and Astellas Pharma. Dr. Zhu has served as a paid consultant for NGM Biopharmaceuticals and Bayer. All other authors have no conflict of interests to disclose. Funding Information: Dr. Sartor has research funding to his institution from AAA, AstraZeneca, Bayer, Merck, Endocyte, Progenics, Novartis, and Janssen. Dr. Sartor has received consulting fees from Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Dendreon, Bristol‐Myers Squibb, Invitae, Merck, Innocrin, Sotio, AAA, AstraZeneca, Bayer, Endocyte, Progenics, Novartis, Janssen, Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Noria Therapeutics, Clovis, Myriad, Noxopharm, Point Biopharm, Tenebio, Theragnostics, Telix, Clarity Pharmaceuticals, and Fusion. Dr. Shore has research support and consulting fees for AbbVie, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Dendreon, Exact Sciences, Fergene, Foundation Medicine, Invitae, Janssen, Merck, Myriad, Pfizer, and Sanofi, Tolmar. Dr. Cheng receives funding from PNW SPORE CA097186, DOD W81XWH‐17‐2‐0043, NIH CA015704, Prostate Cancer Foundation; research funding to her institution from Clovis, Janssen, Sanofi, Medivation/Astellas, Color Foundation, and consulting fees from AstraZeneca. Dr. Antonarakis has served as a paid consultant/advisor for Invitae, Janssen, Pfizer, Sanofi, Dendreon, Merck, Bristol‐Myers Squibb, AstraZeneca, Clovis, Bayer, Constellation, Eli Lilly and Amgen; and has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Bayer, Merck, Bristol‐Myers Squibb, AstraZeneca, ESSA and Constellation. Additionally, Dr. Antonarakis is partially supported by the Patrick Walsh Prostate Cancer Research Fund, the Prostate Cancer Foundation, the NCI Cancer Center Support Grant 5P30 CA006973‐52, the NIH grant R01 CA238384, and the DOD Clinical Consortium award W81XWH‐16‐PCRP‐CCRSA. Dr. Bryce received honoraria from Foundation Medicine, Novartis, Astellas, and Merck. Dr. McKay has served as a paid consultant for Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol‐Myers Squibb, Astellas Medivation, Dendreon, Vividion Therapeutics, Bayer and has research funding to her institution from Pfizer and Bayer. Dr. Burgess has received consulting fees from Johnson and Johnson, honoraria from Exelixis and Bayer, and research funding to his institution from Pfizer and Astellas Pharma. Dr. Zhu has served as a paid consultant for NGM Biopharmaceuticals and Bayer. All other authors have no conflict of interests to disclose. Publisher Copyright: {\textcopyright} 2021 The Authors. The Prostate Published by Wiley Periodicals LLC",

year = "2021",

month = apr,

doi = "10.1002/pros.24123",

language = "English (US)",

volume = "81",

pages = "433--439",

journal = "Prostate",

issn = "0270-4137",

publisher = "Wiley-Liss Inc.",

number = "7",

}

TY - JOUR

T1 - Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer

AU - Ledet, Elisa M.

AU - Burgess, Earle F.

AU - Sokolova, Alexandra O.

AU - Jaeger, Ellen B.

AU - Hatton, Whitley

AU - Moses, Marcus

AU - Miller, Patrick

AU - Cotogno, Patrick

AU - Layton, Jodi

AU - Barata, Pedro

AU - Lewis, Brian E.

AU - Nakazawa, Mari

AU - Zhu, Jason

AU - Dellinger, Beth

AU - Elrefai, Sara

AU - Nafissi, Nellie N.

AU - Egan, Jan B.

AU - Shore, Neal

AU - McKay, Rana R.

AU - Bryce, Alan H.

AU - Cheng, Heather H.

AU - Antonarakis, Emmanuel S.

AU - Sartor, Oliver

N1 - Funding Information: Dr. Sartor has research funding to his institution from AAA, AstraZeneca, Bayer, Merck, Endocyte, Progenics, Novartis, and Janssen. Dr. Sartor has received consulting fees from Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Dendreon, Bristol-Myers Squibb, Invitae, Merck, Innocrin, Sotio, AAA, AstraZeneca, Bayer, Endocyte, Progenics, Novartis, Janssen, Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Noria Therapeutics, Clovis, Myriad, Noxopharm, Point Biopharm, Tenebio, Theragnostics, Telix, Clarity Pharmaceuticals, and Fusion. Dr. Shore has research support and consulting fees for AbbVie, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Dendreon, Exact Sciences, Fergene, Foundation Medicine, Invitae, Janssen, Merck, Myriad, Pfizer, and Sanofi, Tolmar. Dr. Cheng receives funding from PNW SPORE CA097186, DOD W81XWH-17-2-0043, NIH CA015704, Prostate Cancer Foundation; research funding to her institution from Clovis, Janssen, Sanofi, Medivation/Astellas, Color Foundation, and consulting fees from AstraZeneca. Dr. Antonarakis has served as a paid consultant/advisor for Invitae, Janssen, Pfizer, Sanofi, Dendreon, Merck, Bristol-Myers Squibb, AstraZeneca, Clovis, Bayer, Constellation, Eli Lilly and Amgen; and has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Bayer, Merck, Bristol-Myers Squibb, AstraZeneca, ESSA and Constellation. Additionally, Dr. Antonarakis is partially supported by the Patrick Walsh Prostate Cancer Research Fund, the Prostate Cancer Foundation, the NCI Cancer Center Support Grant 5P30 CA006973-52, the NIH grant R01 CA238384, and the DOD Clinical Consortium award W81XWH-16-PCRP-CCRSA. Dr. Bryce received honoraria from Foundation Medicine, Novartis, Astellas, and Merck. Dr. McKay has served as a paid consultant for Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Vividion Therapeutics, Bayer and has research funding to her institution from Pfizer and Bayer. Dr. Burgess has received consulting fees from Johnson and Johnson, honoraria from Exelixis and Bayer, and research funding to his institution from Pfizer and Astellas Pharma. Dr. Zhu has served as a paid consultant for NGM Biopharmaceuticals and Bayer. All other authors have no conflict of interests to disclose. Funding Information: Dr. Sartor has research funding to his institution from AAA, AstraZeneca, Bayer, Merck, Endocyte, Progenics, Novartis, and Janssen. Dr. Sartor has received consulting fees from Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Dendreon, Bristol‐Myers Squibb, Invitae, Merck, Innocrin, Sotio, AAA, AstraZeneca, Bayer, Endocyte, Progenics, Novartis, Janssen, Astellas, Blue Earth Diagnostics, EMD Serono, Pfizer, Constellation, Noria Therapeutics, Clovis, Myriad, Noxopharm, Point Biopharm, Tenebio, Theragnostics, Telix, Clarity Pharmaceuticals, and Fusion. Dr. Shore has research support and consulting fees for AbbVie, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Dendreon, Exact Sciences, Fergene, Foundation Medicine, Invitae, Janssen, Merck, Myriad, Pfizer, and Sanofi, Tolmar. Dr. Cheng receives funding from PNW SPORE CA097186, DOD W81XWH‐17‐2‐0043, NIH CA015704, Prostate Cancer Foundation; research funding to her institution from Clovis, Janssen, Sanofi, Medivation/Astellas, Color Foundation, and consulting fees from AstraZeneca. Dr. Antonarakis has served as a paid consultant/advisor for Invitae, Janssen, Pfizer, Sanofi, Dendreon, Merck, Bristol‐Myers Squibb, AstraZeneca, Clovis, Bayer, Constellation, Eli Lilly and Amgen; and has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Bayer, Merck, Bristol‐Myers Squibb, AstraZeneca, ESSA and Constellation. Additionally, Dr. Antonarakis is partially supported by the Patrick Walsh Prostate Cancer Research Fund, the Prostate Cancer Foundation, the NCI Cancer Center Support Grant 5P30 CA006973‐52, the NIH grant R01 CA238384, and the DOD Clinical Consortium award W81XWH‐16‐PCRP‐CCRSA. Dr. Bryce received honoraria from Foundation Medicine, Novartis, Astellas, and Merck. Dr. McKay has served as a paid consultant for Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol‐Myers Squibb, Astellas Medivation, Dendreon, Vividion Therapeutics, Bayer and has research funding to her institution from Pfizer and Bayer. Dr. Burgess has received consulting fees from Johnson and Johnson, honoraria from Exelixis and Bayer, and research funding to his institution from Pfizer and Astellas Pharma. Dr. Zhu has served as a paid consultant for NGM Biopharmaceuticals and Bayer. All other authors have no conflict of interests to disclose. Publisher Copyright: © 2021 The Authors. The Prostate Published by Wiley Periodicals LLC

PY - 2021/4

Y1 - 2021/4

N2 - BACKGROUND: The goal of this study is to evaluate germline genetic variants in African American men with metastatic prostate cancer as compared to those in Caucasian men with metastatic prostate cancer in an effort to understand the role of genetic factors in these populations.METHODS: African American and Caucasian men with metastatic prostate cancer who had germline testing using multigene panels were used to generate comparisons. Germline genetic results, clinical parameters, and family histories between the two populations were analyzed.RESULTS: A total of 867 patients were included in this retrospective study, including 188 African American and 669 Caucasian patients. There was no significant difference in the likelihood of a pathogenic or likely-pathogenic variants (PV/LPVs) between African American and Caucasian patients (p = .09). African American patients were more likely to have a variant of unknown significance than Caucasians (odds ratio [OR] = 1.95; p < .0001). BRCA1 PV/LPVs were higher in African Americans (OR = 4.86; p = .04). African American patients were less likely to have a PV/LPV in non-BRCA DNA repair genes (OR = 0.30; p = .008). Family history of breast (OR = 2.09; p = .002) or ovarian cancer (OR = 2.33; p = .04) predicted PV/LPVs in Caucasians but not African-Americans. This underscores the limitations of family history in AA men and the importance of personal history to guide germline testing in AA men.CONCLUSIONS: In metastatic prostate cancer patients, PV/LPVs of tested genes did not vary by race, BRCA1 PV/LPVs were more common in the African American subset. However, PV/LPVs in non-BRCA DNA repair genes were less likely to be encountered in African Americans. Family history associated with genetic testing results in Caucasians only.

AB - BACKGROUND: The goal of this study is to evaluate germline genetic variants in African American men with metastatic prostate cancer as compared to those in Caucasian men with metastatic prostate cancer in an effort to understand the role of genetic factors in these populations.METHODS: African American and Caucasian men with metastatic prostate cancer who had germline testing using multigene panels were used to generate comparisons. Germline genetic results, clinical parameters, and family histories between the two populations were analyzed.RESULTS: A total of 867 patients were included in this retrospective study, including 188 African American and 669 Caucasian patients. There was no significant difference in the likelihood of a pathogenic or likely-pathogenic variants (PV/LPVs) between African American and Caucasian patients (p = .09). African American patients were more likely to have a variant of unknown significance than Caucasians (odds ratio [OR] = 1.95; p < .0001). BRCA1 PV/LPVs were higher in African Americans (OR = 4.86; p = .04). African American patients were less likely to have a PV/LPV in non-BRCA DNA repair genes (OR = 0.30; p = .008). Family history of breast (OR = 2.09; p = .002) or ovarian cancer (OR = 2.33; p = .04) predicted PV/LPVs in Caucasians but not African-Americans. This underscores the limitations of family history in AA men and the importance of personal history to guide germline testing in AA men.CONCLUSIONS: In metastatic prostate cancer patients, PV/LPVs of tested genes did not vary by race, BRCA1 PV/LPVs were more common in the African American subset. However, PV/LPVs in non-BRCA DNA repair genes were less likely to be encountered in African Americans. Family history associated with genetic testing results in Caucasians only.

KW - African American

KW - genetics

KW - germline

KW - metastatic prostate cancer

KW - pathogenic variants

KW - racial disparity

UR - http://www.scopus.com/inward/record.url?scp=85103980749&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85103980749&partnerID=8YFLogxK

U2 - 10.1002/pros.24123

DO - 10.1002/pros.24123

M3 - Article

C2 - 33792945

AN - SCOPUS:85103980749

SN - 0270-4137

VL - 81

SP - 433

EP - 439

JO - Prostate

JF - Prostate

IS - 7

ER -

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer

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