African men most at risk of prostate cancer – new study flags genetic causes

A breakthrough study has identified the genetic risk factors that contribute to increased prostate cancer in African men. The study, the largest of its kind, recruited 7,500 men from eastern, southern and west Africa. The study is especially important because African men have a high risk of prostate cancer.

Medical scientist Wenlong Carl Chen explains why the findings are significant and the promise they hold for future treatment.

What did your research look into and why?

Prostate cancer disproportionately affects men of African descent. Studies from the US and African countries report a higher occurrence of prostate cancer in men of African ancestry when compared with men of other ancestries. Men of African and African Caribbean ancestry were also found to be at higher risk of developing a more aggressive form of prostate cancer and of developing it at a younger age when compared with men of European ancestry. Prostate cancer also accounts for nearly one-quarter of all cancer cases diagnosed in Africa.

Our study aimed at uncovering aspects of the genetic architecture of prostate cancer that were specific to men of African descent. In other words, we wanted to understand what it is about African men’s genetic makeup that puts them at higher risk for prostate cancer.

Evidence emerging in the literature suggests that genetic risk factors significantly contribute to the development of prostate cancer. Genetic risks can be put into two groups:

Hereditary risk factors or germline mutations: There are rare genetic mutations in genes, such as BRCA1 and BRCA2, that have been linked to increased risks of developing cancers. Mutations in BRCA2 particularly are linked to higher risks of developing more aggressive prostate cancer.

Single nucleotide polymorphisms or variants: These are common genetic variants that are linked to increased disease risk. Each variant by itself confers a very small increase in risk. However, several variants combined may raise the risk profiles for a disease.

In this study, we assessed the risk contributed by inherited genetic variants to prostate cancer.

Despite the high burden of disease, genetic studies of prostate cancer in continental African populations are limited. The technology needed for these studies is typically very expensive and requires specialised instruments which are very scarce in Africa.

What’s unique about your work?

To better understand the genetic causes of disease, we needed to study diverse populations, particularly African populations. African populations have much higher genetic diversity when compared with other populations. As the place of origin of Homo sapiens, the African population is much older than other populations and has therefore had more time to accumulate genetic variations.

Ours is the largest study to date to investigate the ancestry-specific genetic architectures and disease associations for prostate cancer across multiple regions in sub-Saharan Africa.

Numerous studies like this have been conducted worldwide. However, participation from Africa, both in terms of researchers and study participants, is very low.

How did you go about your research?

Our consortium, the Men of African Descent, Carcinoma of the Prostate (MADCaP), was formed in 2016. Hospitals and universities in five African countries – Nigeria, Ghana, Senegal, Uganda and South Africa – partnered with several US-based universities to form the consortium. The US National Institute of Health provided funding.

The African centres enrolled men with newly diagnosed prostate cancer and, as controls, men of the same population groups who did not have cancer. Demographic, social, economic, and clinical information and bio-samples were collected from the participants.

Our study consisted of 3,963 prostate cancer cases and 3,509 controls. Most bio-sample processing and genotyping was performed in Africa, using a custom genotyping array. A “genotyping array” provides information on hundreds of thousands of DNA variants. This specific one was designed and optimised to capture African genetic variations.

What did you find?

We identified three loci (genetic regions) with a strong association with increased prostate cancer incidence. The lead signals within these loci were common in African populations but were almost absent in non-African populations.

Although these three loci were previously found in other populations, our signals within these loci are unique to African populations. They would not have been found if we had not studied African populations.

There are also differences within Africa. The genetic parts that contribute to prostate cancer risk differ by geographical population.

Why does your research matter?

It is crucial to study diseases in populations with the highest disease burden.

Our findings highlight the importance of studying the possible causes of disease in diverse populations.

We found novel associations by studying the genetics of prostate cancer across Africa. These signals would not have been found in studies done outside Africa.

The genetic diversity of African populations further allowed us to fine-map the regions of associations to better understand what’s driving the signals.

Our findings pave the way for the development of genetic tools that could grade people by their degree of risk.

Another example of this was a 2019 study published in the American Journal of Human Genetics which used genetics to predict the risk of breast cancer. Women placed in higher risk groups would become eligible to enter the UK breast cancer screening programme at a much earlier age.

The results from our study will lay the foundation for the development and implementation of similar tools in an African setting.

By Wenlong Carl Chen, Researcher, University of the Witwatersrand