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Research uncovers genetic clues to high rates of prostate cancer in men with African ancestry – improving risk prediction

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More equitable testing for prostate cancer risk is on the horizon, as researchers report findings from the largest and most genetically diverse study of prostate cancer genes ever conducted.

The study, published in Nature Genetics, identified 187 new genetic variants linked to men’s risk of developing prostate cancer, including several that were only found in men with African ancestry. The findings may help to explain why men with African ancestry are at much greater risk of the disease.

These newly discovered variants mean there is now a panel of 451 ‘risk variants’ that men could be screened for to estimate their risk of developing prostate cancer.

Accurate risk prediction

Predicting risk in men with African ancestry will now be more accurate, correctly identifying an extra 23 per cent of men who will go on to develop prostate cancer, who would have been missed with previous tools.

A dataset was compiled for the research containing DNA from over 944,000 men with European, African, Asian and Hispanic ancestry, including over 150,000 men with prostate cancer.

The 19,391 samples from men with prostate cancer from African ancestry almost doubled the number of such cases ever analysed in previous studies. This makes the findings crucial in efforts to combat high rates of prostate cancer in these men, who are twice as likely to develop the disease than their White European counterparts.

The huge genetic analysis was carried out by a global consortium of scientists, led in the UK by researchers at The Institute of Cancer Research, London, and overall by the Keck School of Medicine of The University of Southern California in the US, with important contributions from The U.S. Veterans Health Administration’s Million Veteran Program and Argonne National Laboratory (US). It was funded by Cancer Research UK, The National Institutes of Health (NIH) in the US, and the Prostate Cancer Foundation.

It also showed that one in six men with African ancestry are highly genetically susceptible to prostate cancer. By the age of 66, one in six men with African ancestry will have already reached a level of risk normally not seen in men until the age of 85.  

Completing the research puzzle

The findings contribute a major part to a research puzzle that’s coming together to reveal how genetic and medical information could be used to spot the men at highest risk of prostate cancer.

By accurately identifying those most at risk, it is hoped that health services could target monitoring to men who are most likely to develop aggressive disease, for whom early detection and diagnosis would have the biggest impact and would potentially save lives.

The UK team at the ICR and The Royal Marsden NHS Foundation Trust are already taking this forward in trials of targeted prostate cancer screening including in men of African ancestry, funded by Prostate Cancer UK.

The discovery of new genetic variants in men with African ancestry also opens avenues of research to discover exactly how these variants increase the risk of prostate cancer, informing risk-reducing strategies.

‘A huge step forward’

Study co-leader Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, and Consultant in Clinical Oncology and Cancer Genetics at The Royal Marsden NHS Foundation Trust, said:

“Prostate cancer affects one in four men with Black African or Caribbean ancestry, compared to one in eight men with White European ancestry. The use of risk stratification will enable us to concentrate screening efforts in those men more likely to have the disease.

“In the past, genetic studies of predisposition to prostate cancer have not been representative – with participants of White European descent far outweighing those of other ancestry. You cannot hope to solve a problem like cancer if you only collect some of the clues. While there is still work to do to in making research truly inclusive and equitable, this study has made huge progress in our ability to find men at higher risk of prostate cancer. I’d like to thank the thousands of men who provided blood samples and health information used to make these important discoveries.”

Study co-leader, Dr Zsofia Kote-Jarai, Senior Scientist at The Institute of Cancer Research, London, said:

"This study represents a huge step forward in our ability to more accurately predict the risk of prostate cancer amongst men with African and African Caribbean ancestry. 

"It is a great example of team science - only possible through ongoing collaboration with our international colleagues. We hope our research will play an important role in reducing health inequalities men face when it comes to prostate cancer - increasing the proportion of prostate cancer cases that are diagnosed early, particularly amongst groups who are currently at higher risk of late diagnosis."

Naser Turabi, Director of Evidence and Implementation at Cancer Research UK said:

“It's great to see more research like this helping clinicians to understand risk in diverse populations. However, more research will be needed to understand if and how polygenic risk scoring could be used in practice to improve how we assess which groups of people may be more at risk of getting certain cancers.”

Christopher Haiman, Director of the USC Center for Genetic Epidemiology at the Keck School of Medicine, said:

“We’re not going to learn everything there is to know about the genetics of prostate cancer by studying only white men. Larger and larger studies, engaging a broader spectrum of populations, are important if we’re going to identify genetic markers of risk and develop risk prediction tools that are equally effective across populations.”

“We’ll continue to improve this risk score, and look for markers that help to distinguish aggressive from less aggressive disease. Clinical trials will be required to evaluate the effectiveness of the risk score in helping doctors and patients make decisions about screening.”

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genetics Ros Eeles prostate cancer personalised medicine PROFILE Genetic testing cancer genetics risk prediction
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