A groundbreaking genetic study conducted in South Africa has unveiled two novel genetic variants that are implicated in breast cancer among black South African women. This discovery marks the first genome-wide association study (GWAS) of breast cancer performed on African women residing on the continent, addressing a critical gap in cancer genomics that has historically favored European and Asian populations. The research, led by scientists from the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at the University of the Witwatersrand, offers unprecedented insights into the genetic underpinnings of breast cancer within African populations, which possess the most genetically diverse human genomes.
Genome-wide association studies are cutting-edge methodologies that systematically scan the entire genome of large cohorts to identify genetic variations that correlate strongly with specific diseases or traits. In this investigation, the SBIMB team performed a comprehensive genomic scan to detect consistent genetic patterns associated with breast cancer in black South African women. They successfully identified significant genetic signals proximity to two genes, RAB27A and USP22, which had not previously been linked to breast cancer risk. RAB27A belongs to the RAS oncogene family, long known for its role in cellular growth and tumorigenesis, while USP22 is recognized for its heightened activity in breast cancer cells and its correlation with adverse clinical outcomes.
The identification of these two genes represents a pivotal advancement in understanding breast cancer biology in women of African descent. Prior to this study, breast cancer genetics research mainly focused on populations of European and Asian ancestry, with African genetic data largely extrapolated from studies involving African American women. African American populations primarily descend from West African genes, which do not fully capture the genetic diversity or cancer risk nuances present in African populations living on the continent. This study therefore fills a crucial void and challenges the applicability of existing genetic risk models in African contexts.
A notable finding of the study is the limited performance of polygenic risk scores (PRS) — tools designed to estimate an individual’s lifetime cancer risk based on multiples genetic markers — in distinguishing South African women with breast cancer from those without. PRSs have shown promise but are predominantly derived from European-ancestry genome data, resulting in diminished accuracy when applied to African populations. This shortcoming underscores the urgent need to develop ancestry-specific genomic tools, tailored to the unique genetic architecture of African populations, to improve cancer risk prediction and ultimately guide prevention strategies effectively.
Breast cancer remains the second most prevalent cancer in South Africa and is the leading malignancy among women worldwide. Genetic factors contribute to approximately 30% of breast cancer cases in South Africa, accentuating the imperative for research rooted in African genomics. This study robustly advocates for increased investment and scientific focus on African-centered genomic research. Such targeted efforts promise to unlock new genetic risk factors and biological pathways that could be pivotal for early detection, diagnosis, and personalized treatment interventions tailored specifically for African populations.
The potential ramifications of these findings extend beyond risk prediction. If further validation studies corroborate the involvement of USP22 and RAB27A in breast cancer pathology, these genes could emerge as novel drug targets within the burgeoning field of precision medicine. The capacity to target specific genes associated with tumor growth and poor prognosis could revolutionize treatment paradigms, allowing clinicians to selectively eradicate malignant cells while minimizing collateral damage to healthy tissues. Such targeted therapies represent the gold standard for improving treatment efficacy and reducing adverse side effects.
Furthermore, recognizing USP22 and RAB27A as biomarkers could enhance clinical decision-making by identifying patients whose tumors exhibit aggressive behavior. This stratification would enable oncologists to tailor treatment intensities and monitoring protocols based on an individual’s genetic profile, optimizing clinical outcomes. Understanding the genetic architecture of breast cancer in African women enriches the broader comprehension of complex disease biology, facilitating the discovery of molecular mechanisms and the development of precision interventions targeted at at-risk groups.
The extensive genomic diversity present in African populations offers a rich resource for uncovering novel genetic risk factors and biological insights. African human genomes display greater variation than any other continental population, yet they remain profoundly underrepresented in global genomic research initiatives. This underrepresentation has resulted in a skewed understanding of disease susceptibility, risk assessment, and treatment development that predominantly benefits non-African populations. Addressing this disparity is critical to ensuring equitable advancements in cancer genomics and clinical care worldwide.
This pioneering study demonstrates that important, hitherto undiscovered genetic risk factors for breast cancer remain concealed within African genomes. As more African-centered genomic research projects are launched, it is expected that additional unique markers and pathways will be uncovered, enriching the global scientific community’s understanding of cancer biology. These discoveries emphasize the necessity of inclusive research that captures the full spectrum of human genetic variation to inform universally applicable medical advances.
The implications extend beyond academic knowledge, heralding a future where African patients benefit from genetics-informed clinical care tailored to their ancestral backgrounds. Such precision medicine initiatives hold the promise of transforming cancer surveillance, prevention, and treatment programs across Africa. This approach aligns with global efforts to reduce health disparities and improve outcomes for historically underserved populations by acknowledging and harnessing genetic diversity in medical research.
Lead researchers stress the importance of continued multidisciplinary collaboration and investment in African genomic infrastructure to expand the scale and depth of studies like this one. Improved access to high-quality genomic data, advanced analytic tools, and bioinformatics expertise will empower local scientists and clinicians to harness genomic insights for personalized medicine. The translational potential embodied in these findings underscores the transformative power of genomics when applied within the context of Africa’s unique population genetics.
In summary, this landmark study breaks new ground by identifying two breast cancer-associated genes specific to black South African women, challenging current paradigms in cancer genetics and risk prediction tools. It spotlights both the profound genetic diversity within African populations and the pressing need for ancestry-specific research to develop precise, effective cancer interventions. Ultimately, these findings illuminate a path towards more equitable, refined genomic medicine that includes all of humanity’s rich genetic heritage.
Subject of Research: Genetic variants associated with breast cancer risk in black South African women
Article Title: Genome-wide association study identifies common variants associated with breast cancer in South African Black women
News Publication Date: 1-Apr-2025
Web References:
- https://www.nature.com/articles/s41467-025-58789-0
- https://www.wits.ac.za/research/sbimb/
- https://h3africa.org/index.php/awi-gen/
References:
Genome-wide association study published in Nature Communications, DOI: 10.1038/s41467-025-58789-0
Keywords: Breast cancer, Cancer genetics, Cancer genomics, Genomic diversity, African genomics, Precision medicine, Genome-wide association study, RAB27A, USP22, Polygenic risk score, African ancestry, Oncology
