Identifying Genetic Variation Associated with Breast Cancer in South African Black Women

Researcher: Mahtaab Hayat is a lecturer and researcher at Wits University. Her research focuses on breast cancer genetics, specifically in South African populations. https://www.nature.com/articles/s41467-025-58789-0

18 June 2026

What Is The Study About?

What if you could predict how likely someone was to develop breast cancer? Not just someone with a history of breast cancer in the family - anybody.

Breast cancer is the leading cause of death in women, globally. We know breast cancer is familial, or inherited. This happens when you inherit a mutation in a high-risk gene, like BRCA1 or BRCA2, and it significantly increases your chance of developing breast cancer. These kind of cases, however, only make up about 10% of all breast cancer cases. How do the remaining cases come about? Through common genetic variation. That is – not one specific mutation that was inherited, but rather a combination of genetic mutations you just happen to have, i.e. many mutations that confer moderate risk that occur together can result in the development of breast cancer. These sporadic cases make up the majority of breast cancer incidents; however, it is difficult to identify. We find these common genetic variants by doing a study called a genome-wide association study (GWAS) that finds statistically associated common genetic variation with breast cancer. So, we look at the entire genome and look for risk variants that are linked to breast cancer.

This study included women with and without breast cancer from Soweto. We read, or genotyped, the entire genome and compared them to see if there were genetic variants that occurred more commonly in women with breast cancer to women without breast cancer.

Why Is This Important?

A lot of genetic research on breast cancer has been done , however, most of it exists in non-African populations. If there are African studies that have been done, they are focused on African American populations. This study was the first resident African GWAS in breast cancer. We know that genetic findings found in non-African populations are not applicable to resident African populations, therefore, we need to carry out studies in resident African populations.

By identifying genetic variation that is associated with breast cancer, we can create something called a polygenic risk score (PRS). A PRS uses the genetic variants found in the GWAS to predict someone’s risk of developing breast cancer based on the genetic variants they have. This can help inform prevention and screening strategies.

What We Know?

In non-African populations, about 200 risk variants have been linked to breast cancer. Using these risk variants, researchers have created polygenic risk scores (PRSs) to help predict the risk of breast cancer. However, many of these risk scores do not work well in populations of African Ancestry and resident African populations. This means that although GWAS in breast cancer have been done, the results cannot be use for resident African populations.

What Was Discovered?

Usually, GWAS for breast cancer are done in large study cohorts. An example of a study done in 2016 included 122 977 patients with breast cancer and 105 974 without. This study identified 65 risk variants. In contrast, our study only had 2485 women with breast cancer and 1101 without. Although our sample was small in comparison to European studies, we identified two risk variants associated with breast cancer. These variants were not found to be associated with breast cancer in previous studies, however, there are some links to cancerous properties.

The first risk variant (rs7181788) was found between the genes UNC13C and RAB27A on chromosome 15. These two genes are involved in cellular growth (RAB27A) and tumour growth/progression (UNC13C).

The second (rs899342) was identified in the gene USP22 on chromosome 17. This gene was found to have been associated with poor survival in patients with breast cancer. It also contributes to chemotherapy resistance in patients with triple negative breast cancer tumours.

The Future/Possible Solutions

The future for GWAS in breast cancer in South Africa specifically is to first carry out more studies in resident African populations. This will allow us to grow the amount of data we have, but also to generate population-specific data within South Africa because our country is so genetically diverse. Once we have enough data, we can start creating PRSs and use them in a clinical setting. PRSs will let us predict the risk of any individual’s risk for breast cancer. Given an individual’s risk, health care practitioners can design appropriate screening strategies to catch the cancer before it spreads and becomes difficult to treat. This will, hopefully, save lives and increase quality of life for many people.