BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry

Tara M Friebel^{1

2}, Irene L Andrulis^{3

4}, Judith Balmaña⁵, Amie M Blanco⁶, Fergus J Couch⁷, Mary B Daly⁸, Susan M Domchek⁹, Douglas F Easton^{10

11}, William D Foulkes¹², Patricia A Ganz¹³, Judy Garber¹⁴, Gord Glendon³, Mark H Greene¹⁵, Peter J Hulick^{16

17}, Claudine Isaacs¹⁸, Rachel C Jankowitz¹⁹, Beth Y Karlan²⁰, Judy Kirk²¹, Ava Kwong^{22

23

24}, Annette Lee²⁵, Fabienne Lesueur^{26

27

28

29}, Karen H Lu³⁰, Katherine L Nathanson⁹, Susan L Neuhausen³¹, Kenneth Offit^{32

33}, Edenir I Palmero^{34

35}, Priyanka Sharma³⁶, Marc Tischkowitz^{12

37}, Amanda E Toland³⁸, Nadine Tung³⁹, Elizabeth J van Rensburg⁴⁰, Ana Vega^{41

42

43}, Jeffrey N Weitzel⁴⁴, Gemo Study Collaborators²⁷, Kent F Hoskins⁴⁵, Tara Maga⁴⁵, Michael T Parsons⁴⁶, Lesley McGuffog¹¹, Antonis C Antoniou¹¹, Georgia Chenevix-Trench⁴⁶, Dezheng Huo⁴⁷, Olufunmilayo I Olopade⁴⁷, Timothy R Rebbeck^{1

2}

Affiliations

¹ Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
² Dana-Farber Cancer Institute, Boston, Massachusetts.
³ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁵ High Risk and Cancer Prevention Group, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, Barcelona, Spain.
⁶ Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, California.
⁷ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
⁸ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
⁹ Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
¹⁰ Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
¹¹ Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
¹² Departments of Human Genetics and Oncology, Program in Cancer Genetics, McGill University, Montréal, Quebec, Canada.
¹³ Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, Schools of Medicine and Public Health, UCLA, Los Angeles, California.
¹⁴ Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts.
¹⁵ Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, Bethesda, Maryland.
¹⁶ Center for Medical Genetics, NorthShore University HealthSystem, Evanston, Illinois.
¹⁷ The University of Chicago Pritzker School of Medicine, Chicago, Illinois.
¹⁸ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
¹⁹ Division of Hematology/Oncology, Department of Medicine, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
²⁰ Cedars-Sinai Medical Center, Womens Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
²¹ Familial Cancer Service, Weatmead Hospital, Wentworthville, New South Wales, Australia.
²² Cancer Genetics Centre, Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong, China.
²³ Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.
²⁴ Department of Surgery, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong, China.
²⁵ The Feinstein Institute for Medical Research, Manhasset, New York.
²⁶ Genetic Epidemiology of Cancer team, Inserm, Paris, France.
²⁷ Service de Génétique, Institut Curie, Paris, France.
²⁸ Institut Curie, Paris, France.
²⁹ Mines ParisTech, Fontainebleau, France.
³⁰ Department of Gynecologic Oncology and Clinical Cancer Genetics Program, University of Texas MD Anderson Cancer Center, Houston, Texas.
³¹ Department of Population Sciences, Beckman Research Institute of City of Hop, Duarte, California.
³² Department of Cancer Biology and Genetics, Clinical Genetics Research Lab, Memorial Sloan-Kettering Cancer Center, New York, New York.
³³ Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
³⁴ Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
³⁵ Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, São Paulo, Brazil.
³⁶ Division of Oncology, Department of Internal Medicine, University of Kansas Medical Center, Westwood, Kansas.
³⁷ Department of Medical Genetics, Addenbrookes Treatment Centre, Addenbrookes Hosptital, University of Cambridge, Cambridge, UK.
³⁸ Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio.
³⁹ Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
⁴⁰ Department of Genetics, University of Pretoria, Arcadia, South Africa.
⁴¹ Fundación Pública Galega Medicina Xenómica, Santiago De Compostela, Spain.
⁴² Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago De Compostela, Spain.
⁴³ Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
⁴⁴ Clinical Cancer Genetics, City of Hope, Duarte, California.
⁴⁵ Department of Medicine, University of Illinois, Chicago, Illinois.
⁴⁶ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁴⁷ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois.

PMID: 31112363
PMCID: PMC6764847
DOI: 10.1002/humu.23804

BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry

Tara M Friebel et al. Hum Mutat. 2019 Oct.

. 2019 Oct;40(10):1781-1796.

doi: 10.1002/humu.23804. Epub 2019 Jul 3.

Authors

Affiliations

¹ Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
² Dana-Farber Cancer Institute, Boston, Massachusetts.
³ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁵ High Risk and Cancer Prevention Group, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, Barcelona, Spain.
⁶ Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, California.
⁷ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
⁸ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
⁹ Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
¹⁰ Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
¹¹ Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
¹² Departments of Human Genetics and Oncology, Program in Cancer Genetics, McGill University, Montréal, Quebec, Canada.
¹³ Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, Schools of Medicine and Public Health, UCLA, Los Angeles, California.
¹⁴ Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts.
¹⁵ Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, Bethesda, Maryland.
¹⁶ Center for Medical Genetics, NorthShore University HealthSystem, Evanston, Illinois.
¹⁷ The University of Chicago Pritzker School of Medicine, Chicago, Illinois.
¹⁸ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
¹⁹ Division of Hematology/Oncology, Department of Medicine, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
²⁰ Cedars-Sinai Medical Center, Womens Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
²¹ Familial Cancer Service, Weatmead Hospital, Wentworthville, New South Wales, Australia.
²² Cancer Genetics Centre, Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong, China.
²³ Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.
²⁴ Department of Surgery, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong, China.
²⁵ The Feinstein Institute for Medical Research, Manhasset, New York.
²⁶ Genetic Epidemiology of Cancer team, Inserm, Paris, France.
²⁷ Service de Génétique, Institut Curie, Paris, France.
²⁸ Institut Curie, Paris, France.
²⁹ Mines ParisTech, Fontainebleau, France.
³⁰ Department of Gynecologic Oncology and Clinical Cancer Genetics Program, University of Texas MD Anderson Cancer Center, Houston, Texas.
³¹ Department of Population Sciences, Beckman Research Institute of City of Hop, Duarte, California.
³² Department of Cancer Biology and Genetics, Clinical Genetics Research Lab, Memorial Sloan-Kettering Cancer Center, New York, New York.
³³ Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
³⁴ Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
³⁵ Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, São Paulo, Brazil.
³⁶ Division of Oncology, Department of Internal Medicine, University of Kansas Medical Center, Westwood, Kansas.
³⁷ Department of Medical Genetics, Addenbrookes Treatment Centre, Addenbrookes Hosptital, University of Cambridge, Cambridge, UK.
³⁸ Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio.
³⁹ Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
⁴⁰ Department of Genetics, University of Pretoria, Arcadia, South Africa.
⁴¹ Fundación Pública Galega Medicina Xenómica, Santiago De Compostela, Spain.
⁴² Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago De Compostela, Spain.
⁴³ Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
⁴⁴ Clinical Cancer Genetics, City of Hope, Duarte, California.
⁴⁵ Department of Medicine, University of Illinois, Chicago, Illinois.
⁴⁶ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁴⁷ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois.

PMID: 31112363
PMCID: PMC6764847
DOI: 10.1002/humu.23804

Abstract

BRCA1 and BRCA2 (BRCA1/2) pathogenic sequence variants (PSVs) confer elevated risks of multiple cancers. However, most BRCA1/2 PSVs reports focus on European ancestry individuals. Knowledge of the PSV distribution in African descent individuals is poorly understood. We undertook a systematic review of the published literature and publicly available databases reporting BRCA1/2 PSVs also accessed the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) database to identify African or African descent individuals. Using these data, we inferred which of the BRCA PSVs were likely to be of African continental origin. Of the 43,817 BRCA1/2 PSV carriers in the CIMBA database, 469 (1%) were of African descent. Additional African descent individuals were identified in public databases (n = 291) and the literature (n = 601). We identified 164 unique BRCA1 and 173 unique BRCA2 PSVs in individuals of African ancestry. Of these, 83 BRCA1 and 91 BRCA2 PSVs are of likely or possible African origin. We observed numerous differences in the distribution of PSV type and function in African origin versus non-African origin PSVs. Research in populations of African ancestry with BRCA1/2 PSVs is needed to provide the information needed for clinical management and decision-making in African descent individuals worldwide.

Keywords: African ancestry; BRCA1; BRCA2; mutation; pathogenic sequence variant.

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Figures

**Figure 1**
Summary of Literature Review Used in This Report for *BRCA1* (GenBank reference sequence: NG_005905.2) or *BRCA2* (GenBank reference sequence NG_012772.3)

**Figure 2**
*BRCA1* (GenBank reference sequence: NG_005905.2) PSVs by Determination of African Origin and Self-Identification. a. Likely or Possible African Origin, b. Unlikely African Origin.

See this image and copyright information in PMC

References

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BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry

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BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry

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