A recent genome-wide association study has identified two novel genetic risk loci linked to breast cancer susceptibility in Black South African women, marking a significant advancement in understanding the genetic underpinnings of breast cancer within this population. This discovery holds the potential to improve risk prediction and guide the development of targeted therapies tailored to women of African ancestry.
The study revealed two distinct genetic regions associated with increased breast cancer risk: one located between the UNC13C and RAB27A genes on chromosome 15, identified by the marker rs7181788, and another within the USP22 gene on chromosome 17, marked by rs899342. Neither of these loci had been previously connected to breast cancer, highlighting the importance of exploring diverse genetic backgrounds to uncover unique risk factors.
Historically, much of the genetic research on breast cancer risk has focused on populations of European and Asian descent, as well as African American women, who predominantly trace their ancestry to West Africa. However, this leaves a critical gap in understanding breast cancer genetics among Black South African women, whose genetic makeup and environmental exposures may differ substantially. Previous attempts to apply polygenic risk scores developed from European cohorts to South African populations have been largely unsuccessful, underscoring the need for ancestry-specific genetic tools.
The study was conducted using a large cohort of Black South African women, comprising 2,485 individuals diagnosed with breast cancer and 1,101 matched controls without the disease. Participants were drawn from two major research collaborations: the Johannesburg Cancer Study and the Africa Wits-INDEPTH Partnership for Genomic Research Study. This robust sample allowed researchers to conduct a comprehensive genome-wide association analysis specifically tailored to this population.
Interestingly, when researchers attempted to replicate their findings in populations of West African ancestry, the genetic associations identified in the South African cohort did not hold. This lack of replication suggests substantial genetic heterogeneity across different African populations, reflecting the continent’s vast genetic diversity. It also indicates that risk factors identified in one African population may not be universally applicable to others, further emphasizing the necessity of region-specific genetic studies.
Furthermore, when comparing the predictive power of polygenic risk models, only a very small proportion 0.79% of data variance in European ancestry breast cancer patients could be explained using the same model. This stark difference demonstrates that polygenic risk models based on European populations have limited effectiveness in accurately assessing breast cancer risk for women of African descent, highlighting the need for tailored approaches.
The discovery of these two novel risk loci offers promising avenues for future research. With further validation and exploration, these genetic regions could become important targets for new therapies designed to improve outcomes for Black South African women with breast cancer. Targeted treatments aimed at genetic drivers of the disease could potentially lead to more effective management of aggressive cancer types, which are often more prevalent and deadly in women of African ancestry.
This study underscores the critical importance of expanding genomic research to include diverse populations, particularly those historically underrepresented in genetic studies. Such inclusion is essential not only for improving risk prediction and treatment but also for addressing existing disparities in cancer outcomes.
Moving forward, researchers advocate for continued and expanded genomic investigations in African populations. Larger sample sizes, broader geographic representation, and integration of environmental and lifestyle factors will be key to fully understanding the genetic architecture of breast cancer in these groups. In doing so, the scientific community can help pave the way for precision medicine approaches that are inclusive and effective for all populations, ultimately reducing the global burden of breast cancer.
