Researchers including those from Wits have identified the genetic risk factors that contribute to prostate cancer in a diverse group of African men.

Although research and treatment are scant, this first large-scale African genomics study could signal new treatment possibilities.

“From the literature, men of African descent have a much higher risk of developing prostate cancer during their lifetime. It tends to develop at an earlier age and is more aggressive. But we have only really studied prostate cancer in European populations. By studying genetic risk factors in African men – at a large scale - we can one day refine screening and treatment,” says Dr Carl Chen, a researcher at the Sydney Brenner Institute for Molecular Biosciences (SBIMB) at Wits University and the second author of the paper.

The study, titled Heterogenous genetic architecture of prostate cancer susceptibility in sub-Saharan Africa, published in the high impact Nature Genetics journal, enrolled almost 8000 African men (half had prostate cancer, and the other comprised a control group) from five African countries across West, East and Southern Africa.

This is the largest study of this kind to date.

Chen says, “We identified three loci, or genetic regions, strongly associated with increased prostate incidence. The top ‘signals’ within these three loci are unique to African populations and would not have been found if we didn’t study African populations."

Notably, regional differences exist in the strength of the ‘signals’ between East, West and Southern Africa.

This means that there are different types of risks across Africa.

Professor Michèle Ramsay, Director of the SBIMB, says, “The findings from this study will lay the foundation to develop models for risk prediction using genetic data to improve the treatment of prostate cancer. Prostate cancer screening is virtually non-existent in Africa, allowing for the study of the natural history and genetic associations of prostate cancer in the absence of early detection."

Ramsay says that the paper also aligns with SBIMB’s strategic vision for Precision Medicine by working to better understand the molecular risk factors of common African cancers.

“We aim to uncover region-specific genetic mutations and variations, leading to more accurate, culturally relevant treatments that address the unique genetic diversity of African populations, ultimately improving cancer care and outcomes across the continent," says Ramsay.

To address the need for unique genetic diversity in African populations for the African prostate cancer study, the SBIMB Biobank played a significant role by processing approximately 2,000 biosamples - nearly a quarter of the total study sample.

Currently, the Biobank holds about 30,000 DNA samples from participants of African heritage, gathered from numerous research projects.

Ms Natalie Smyth, SBIMB Biobank and Laboratory Manager, says, “The research infrastructure is crucial for supporting large-scale genetic research in Africa."

Unique genetic variations help explain why current prostate cancer screening methods are less effective for African men.

Certain prostate cancer variations are not found in European populations, which contributes to higher disease rates in unscreened African groups because European data has thus far guided interventions in Africa.

This study highlights the importance of genetic research in diverse populations.

Future research should use ancestry-specific data to address differences in genomic medicine.

The study is a product of the Men of African Descent and Carcinoma of the Prostate (MADCaP) network, which includes African and US investigators who have explored prostate cancer causes, risks, screening and clinical management over the past 20 years.

“MADCaP is guided by the development of world-class research that affects African populations. Bio-sampling, genotyping and data management are performed in Africa to build local capacity for cancer research," says Dr Timothy Rebbeck from the Dana Farber Cancer Institute, Harvard, a leader in the study.

"The MADCaP network ensures that data from different centres, including both risk factors and clinical data, are consistent. They hold meetings to encourage communication between clinicians and bioinformaticians. The MADCaP network has also developed a new genotyping array specifically designed to identify genetic links to cancer in African populations, in addition to enhancing research capabilities.”

Chen says that the findings of the study reveal that prostate cancer is a complex disease and that studying this in diverse populations with high disease burden is critical because they may possess genetic risk variants absent in other populations.

Source: University of the Witwatersrand