Understanding the Genetic Factors Behind Breast Cancer in Sub-Saharan Africa
Breast cancer is a significant health concern, particularly for women around the world. It is the most common cancer among women globally and a leading cause of cancer-related deaths in sub-Saharan Africa. The risk factors for developing breast cancer include being female, increasing age, being overweight, alcohol consumption, and genetic factors. These elements contribute to the likelihood of an individual developing the disease.
Genome-wide association studies (GWAS) have become a crucial tool in understanding the genetic underpinnings of various diseases, including breast cancer. These studies scan the entire genome to identify common genetic variants that may influence the risk of developing certain traits or diseases. Since their introduction in 2005, GWAS have provided valuable insights into diagnosis, screening, and prediction of diseases. Recent findings have led to the development of prediction tools that help identify individuals at high risk of developing diseases. One such tool is genetic risk scores, also known as polygenic risk scores, which estimate disease predisposition based on multiple genetic variants.
However, most of this research has been conducted on populations of European ancestry, which presents a challenge due to differences in genetic diversity and environmental factors across the globe. In Africa, the genetic diversity observed is even greater across populations. This gap in research prompted a team of researchers from Wits University, Sydney Brenner Institute for Molecular Bioscience, and collaborators at the South African National Cancer Registry to conduct the first genome-wide association study of breast cancer in a sub-Saharan African population.
Identifying Population-Specific Genetic Variants
The study compared genetic variation between women with breast cancer and those without, aiming to find variants that occur more frequently in cancer patients. The results identified two genomic variants near the RAB27A and USP22 genes that contribute to the risk of breast cancer in South African black women. These genetic variants had not previously been associated with breast cancer in non-African populations.
This finding highlights the importance of identifying population-specific genetic variants, especially in understudied populations. Different populations may carry unique variants that affect breast cancer risk differently. Risk variants found in other populations might not be present in African populations. This underscores the need for research efforts and risk scores to be tailored to different populations, including those in Africa.
Comparative Analysis of DNA Samples
The study involved DNA samples from 2,485 women with breast cancer and 1,101 women without breast cancer. All participants were residents of Soweto in South Africa. The breast cancer cases were recruited to the Johannesburg Cancer Study over 20 years, while the controls came from the Africa Wits-INDEPTH Partnership for Genomic Research study.
The analysis used technology called a DNA chip, specifically designed by the H3Africa consortium to capture genetic variants within African populations. By comparing genetic variation in women with breast cancer and those without, the study identified two genetic variants that contribute to the risk of breast cancer in South African black women. These variants are located near genes involved in the growth of breast cancer cells, the ability of cancer cells to metastasise, and tumour growth in different cancers.
Evaluating Polygenic Risk Scores
The study also applied polygenic risk scores to the African dataset. This method estimates the risk of breast cancer for an individual based on the presence of risk variants. The risk score used was derived from European populations. When applied to the African dataset, it showed reduced accuracy in predicting breast cancer compared to its performance in European populations.
Future Directions and Implications
This study marks the first large-scale genome-wide association analysis in sub-Saharan Africa to identify genetic factors influencing breast cancer risk. However, the sample size of fewer than 4,000 participants is significantly smaller than larger breast cancer genetic studies involving over 200,000 cases and controls. This highlights the urgent need for greater research efforts and increased participation from sub-Saharan African populations.
The results from this and future studies will aid doctors in screening patients and identifying those at high risk. Once high-risk individuals are identified, they can be offered more frequent check-ups and preventive measures, allowing for early detection or even prevention of breast cancer.
Further research is needed to understand how these genes increase breast cancer risk and improve prediction methods. Notably, European-derived polygenic risk scores did not accurately predict breast cancer in the African dataset, performing worse than in non-African datasets. These results align with previous findings for other diseases.
Researchers are involved in a global study called Confluence, which examines the genetics of breast cancer across many populations, including African ones.