Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa
Background. Hereditary breast cancer is characterised by the presence of a pathogenic sequence variant passed from one generation to the next. These cancers are aggressive, develop early, and account for 5 - 10% of all breast cancer cases. In South Africa (SA), the common variants that predispo...
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South African Medical Association
2024-05-01
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| Series: | South African Medical Journal |
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| Online Access: | https://samajournals.co.za/index.php/samj/article/view/1094 |
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| author | M Makhetha C Aldous N Chabilal |
| author_facet | M Makhetha C Aldous N Chabilal |
| author_sort | M Makhetha |
| collection | DOAJ |
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Background. Hereditary breast cancer is characterised by the presence of a pathogenic sequence variant passed from one generation to the next. These cancers are aggressive, develop early, and account for 5 - 10% of all breast cancer cases. In South Africa (SA), the common variants that predispose to hereditary breast cancer have been well documented among white patients and form part of screening panels during targeted testing. For non-white patients, common variants are not well understood, and as such, all populations are offered the same test optimised for white patients. This carries a risk of misdiagnosis, the consequences of which include recurrence and increased mortality.
Objectives. To retrospectively describe genetic trends in the black African and Indian breast cancer patients from KwaZulu-Natal Province, SA.
Methods. We reviewed clinical and genetic data of breast cancer and high-risk patients who consulted at Inkosi Albert Luthuli Central Hospital between 2011 and 2021. Inclusion criteria were based on clinical and demographic characteristics as defined by SA clinical guidelines.
Results. Black African patients were young (mean 37.6 years, standard deviation 11.16) and had the majority of triple-negative tumours (37.5%). Indians represented 50% of bilateral breast cancers and of high-risk individuals. We identified 30 pathogenic BRCA1/2 sequence variants, four large genomic rearrangements and 13 variants of unknown significance. Twenty black patients carried 12, 13 white patients carried 4, 25 Indian patients carried 16, and 3 coloured patients carried 3 pathogenic sequence variants. The most frequent variants were BRCA2 c.5771_5774del, p.Ile1924fs among black patients, BRCA2 c.7934del, p.Arg2645fs among white patients, and BRCA2 c.8754+1G>A among Indian patients. None of the founder mutations common in white patients was reported in either black, Indian or coloured patients, which explains why black, Coloured and Indian SA patients consistently test negative during targeted screening.
Conclusion. This study highlights unique genetic trends for SA populations and the need for more inclusive targeted tests that are optimal for these populations.
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| format | Article |
| id | doaj-art-eecb00f346cf41d3892c7601c52e310e |
| institution | Kabale University |
| issn | 0256-9574 2078-5135 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | South African Medical Association |
| record_format | Article |
| series | South African Medical Journal |
| spelling | doaj-art-eecb00f346cf41d3892c7601c52e310e2025-02-10T12:26:04ZengSouth African Medical AssociationSouth African Medical Journal0256-95742078-51352024-05-01114610.7196/SAMJ.2024.v114i6.1094Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South AfricaM Makhetha0C Aldous1N Chabilal2Department of Clinical Medicine, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South AfricaDepartment of Genetics, Inkosi Albert Luthuli Central Hospital, Durban, South AfricaDepartment of Clinical Medicine, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Background. Hereditary breast cancer is characterised by the presence of a pathogenic sequence variant passed from one generation to the next. These cancers are aggressive, develop early, and account for 5 - 10% of all breast cancer cases. In South Africa (SA), the common variants that predispose to hereditary breast cancer have been well documented among white patients and form part of screening panels during targeted testing. For non-white patients, common variants are not well understood, and as such, all populations are offered the same test optimised for white patients. This carries a risk of misdiagnosis, the consequences of which include recurrence and increased mortality. Objectives. To retrospectively describe genetic trends in the black African and Indian breast cancer patients from KwaZulu-Natal Province, SA. Methods. We reviewed clinical and genetic data of breast cancer and high-risk patients who consulted at Inkosi Albert Luthuli Central Hospital between 2011 and 2021. Inclusion criteria were based on clinical and demographic characteristics as defined by SA clinical guidelines. Results. Black African patients were young (mean 37.6 years, standard deviation 11.16) and had the majority of triple-negative tumours (37.5%). Indians represented 50% of bilateral breast cancers and of high-risk individuals. We identified 30 pathogenic BRCA1/2 sequence variants, four large genomic rearrangements and 13 variants of unknown significance. Twenty black patients carried 12, 13 white patients carried 4, 25 Indian patients carried 16, and 3 coloured patients carried 3 pathogenic sequence variants. The most frequent variants were BRCA2 c.5771_5774del, p.Ile1924fs among black patients, BRCA2 c.7934del, p.Arg2645fs among white patients, and BRCA2 c.8754+1G>A among Indian patients. None of the founder mutations common in white patients was reported in either black, Indian or coloured patients, which explains why black, Coloured and Indian SA patients consistently test negative during targeted screening. Conclusion. This study highlights unique genetic trends for SA populations and the need for more inclusive targeted tests that are optimal for these populations. https://samajournals.co.za/index.php/samj/article/view/1094Breast cancerPathogenic sequence variantsSouth AfricaGenetic TestingBRCA1/2 |
| spellingShingle | M Makhetha C Aldous N Chabilal Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa South African Medical Journal Breast cancer Pathogenic sequence variants South Africa Genetic Testing BRCA1/2 |
| title | Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa |
| title_full | Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa |
| title_fullStr | Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa |
| title_full_unstemmed | Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa |
| title_short | Genetic trends and common BRCA1/2 pathogenic sequence variants in black African and Indian breast cancer patients presenting at Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa |
| title_sort | genetic trends and common brca1 2 pathogenic sequence variants in black african and indian breast cancer patients presenting at inkosi albert luthuli central hospital kwazulu natal south africa |
| topic | Breast cancer Pathogenic sequence variants South Africa Genetic Testing BRCA1/2 |
| url | https://samajournals.co.za/index.php/samj/article/view/1094 |
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