Genome-wide association study identifies common variants associated with breast cancer in South African Black women
Genome-wide association studies (GWAS) have characterized the contribution of common variants to breast cancer (BC) risk in populations of European ancestry, however GWAS have not been reported in resident African populations. This GWAS included 2485 resident African BC cases and 1101 population matched controls. Two risk loci were identified, located between UNC13C and RAB27A on chromosome 15 (rs7181788, p = 1.01 × 10<sup>-08</sup>) and in USP22 on chromosome 17 (rs899342, p = 4.62 × 10<sup>-08</sup>). Several genome-wide significant signals were also detected in hormone receptor subtype analysis. The novel loci did not replicate in BC GWAS data from populations of West Africa ancestry suggesting genetic heterogeneity in different African populations, but further validation of these findings is needed. A European ancestry derived polygenic risk model for BC explained only 0.79% of variance in our data. Larger studies in pan-African populations are needed to further define the genetic contribution to BC risk.
Authors
- Debbie Bradshaw (ORCID: https://orcid.org/0000-0002-3588-2184)
- Christopher G. Mathew (ORCID: https://orcid.org/0000-0003-4178-1838)
- Chantal Babb de Villiers (ORCID: https://orcid.org/0000-0003-1334-1819)
- Wenlong Carl Chen (ORCID: https://orcid.org/0000-0002-3248-4906)
- Charles Curtis (ORCID: https://orcid.org/0000-0002-2992-1941)
- Cathryn M. Lewis (ORCID: https://orcid.org/0000-0002-8249-8476)
- Michèle Ramsay (ORCID: https://orcid.org/0000-0002-4156-4801)
- Freddy Sitas (ORCID: https://orcid.org/0000-0001-9679-1481)
- Robert Newton (ORCID: https://orcid.org/0000-0001-6715-9153)
- Elvira Singh (ORCID: https://orcid.org/0000-0003-1259-2122)
- Tim Waterboer (ORCID: https://orcid.org/0000-0002-0616-6963)
- Jean‐Tristan Brandenburg (ORCID: https://orcid.org/0000-0003-0197-2648)
- M Hayat (ORCID: https://orcid.org/0000-0003-4723-1407)
- Sang Hyuck Lee (ORCID: https://orcid.org/0000-0002-5610-033X)
- Mazvita Muchengeti
Institutions
- National Health Laboratory Service (ZA)
- South African Medical Research Council (ZA)
- University of Technology Sydney (AU)
- German Cancer Research Center (DE)
- King's College London (GB)
- University of the Witwatersrand (ZA)
- South London and Maudsley NHS Foundation Trust (GB)
- Heidelberg University (DE)
- Stellenbosch University (ZA)
- UNSW Sydney (AU)
- University of York (GB)
- Uganda Virus Research Institute (UG)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-14
- DOI
- https://doi.org/10.1038/s41467-025-58789-0
- Citations
- 11
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 19.99
Funders
- Government of the United Kingdom
- National Institute for Health and Care Research
- King's College London
- South African Medical Research Council
- Cancer Association of South Africa
- National Health Laboratory Service
- National Institutes of Health
- NIHR Maudsley Biomedical Research Centre
- Medical Research Council