South African study identifies two new breast cancer genes in black women
- Wits University
Genetic factors contribute to some 30% of breast cancer cases in SA, necessitating investment in genomic research in African contexts.
A seminal genetic study published in Nature Communication has discovered two genetic variants linked to breast cancer in black South African women, deepening knowledge about the genetic basis for this disease in African populations.
The genome-wide association study (GWAS) of breast cancer is the first to have been done in African women living on the continent.
A GWAS is a powerful research method that scans the entire DNA of many people to find genetic differences associated with a specific disease or trait.
In this case, the scientists at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) scanned for breast cancer and found consistent genetic patterns in black South African women.
The SBIMB researchers discovered genetic signals around the gene RAB27A, a member of the RAS oncogene family, and USP22, a gene which is highly active in breast cancer cells and associated with a poor health prognosis.
“These genes have not been associated with the disease before, which is an important advance in understanding breast cancer risk and biology in women of African ancestry,” says Dr Mahtaab Hayat, the lead author of the study.
The two new genetic variants were identified in black South African women with breast cancer enrolled in the Johannesburg Cancer Study, compared to women without cancer in the Africa Wits-INDEPTH Partnership for Genomic Research (AWI-Gen) study.
Until now, most breast cancer genetics research has focused on European and Asian populations, with studies of African ancestry limited primarily to African- American women, who largely descend from West African populations.
A tool that estimates lifetime cancer risk based on DNA, the polygenic risk score (PRS), performed poorly in distinguishing South African women with breast cancer from those without.
“This is because most PRSs were developed in European populations, and their inaccuracy in African populations highlights the urgent need for ancestry-specific tools in cancer risk prediction,” says Dr Jean-Tristan Brandenburg, also in the SBIMB and a lead author.
Breast cancer is the second most common cancer in South Africa and the most common cancer in women globally, with genetic factors contributing to about 30% of cases. “Our study makes a compelling case for investing in genomic research rooted in African contexts,” notes Hayat.
The potential for precision medicine
If further studies confirm these findings, the USP22 and RAB27A genes could be specific targets for new drugs. “We could potentially target harmful cancer cells while sparing healthy tissue, which is ideally what we want when administering cancer treatment,” says Distinguished Professor at the SBIMB, Chris Mathew, and a lead project investigator.
Furthermore, if a specific gene is associated with poorer survival, it can be used as a biomarker to identify more aggressive cancers and help predict which patients may need more intensive treatment and monitoring.
Understanding the genetic architecture of complex diseases helps scientists figure out the biological processes leading to these conditions and find drug targets and treatments for groups of individuals with similar disease risk profiles.
Genomic diversity in Africa is unparalleled
African populations have more genetic variation than any other population in the world, but they have been significantly underrepresented in genomic research. This means that the global understanding of disease risk, and the tools and treatment developed from it, is limited.
“The study reveals that more people can benefit from genetic discoveries. It proves that new risk factors are still out there, waiting to be found,” says Hayat.