Two genetic variants linked to breast cancer discovered in black South African women

Two genetic variants linked to breast cancer discovered in black South African women

Genetic factors contribute to around 30% of breast cancer cases in SA, requiring investment in genomic research in African contexts.

A landmark genetic study published inNature communicationhas discovered two genetic variants linked to breast cancer in black South African women, deepening knowledge of the genetic basis for this disease in African populations.

The breast cancer genome-wide association study (GWAS) is the first to be conducted in African women on the continent.

A GWAS is a powerful research method that scans all of many people's DNA to find genetic differences associated with a particular disease or trait.

In this case, scientists at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) scanned for breast cancer and found consistent genetic patterns in black South African women.

SBIMB researchers discovered genetic signals surrounding the gene Rab27a, a member of the Ras oncogene family, and USP22, a gene that is highly active in breast cancer cells and is associated with poor health prognosis.

These genes have not previously been linked to the disease, marking an important advance in understanding breast cancer risk and biology in women of African ancestry. “

Dr. Mahtaab Hayat, 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 with women without cancer in the Wits Undepth Partnership for Genomics Research (AWI-Gen) Africa study.

To date, most breast cancer genetics research has focused on European and Asian populations, with studies of African ancestry limited primarily to African American women largely descended from West African populations.

A tool that estimates lifetime cancer risk based on DNA, the polygenic risk score (PRS), has performed poorly at distinguishing South African women with breast cancer from those without it.

“This is because most PRSs were developed in European populations, and their inaccuracies in African populations highlight the urgent need for ancestral ancestry in predicting cancer risks,” says Dr. Jean-Tristan Brandenburg, also in SBIMB and a senior author.

Breast cancer is the second most common cancer in South Africa and the most common cancer in women worldwide, with genetic factors contributing to approximately 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 results, the USP22 and Rab27a genes could be specific targets for new drugs. “We could potentially target harmful cancer cells while sparing healthy tissue.

If a particular gene is associated with worse survival, it can be used as a biomarker to identify more aggressive cancers and predict which patients may need more intensive treatment and monitoring.

Understanding the genetic architecture of complex diseases helps scientists find the biological processes that lead to these diseases and find drug targets and treatments for groups of people with similar disease risk profiles.

The genomic diversity in Africa is unprecedented

African populations have more genetic variation than any other population in the world, yet have been significantly underrepresented in genomic research. This means that global understanding of disease risk and the tools and treatment developed from it are limited.

"The study shows that more people can benefit from genetic discoveries. It proves that new risk factors are still out there waiting to be found," says Hayat.

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