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Image: DNA strand
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 of African descent. The findings may help explain why men of African descent are at a much higher risk of contracting 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 forecast
Risk prediction in men of African descent will now be more accurate, correctly identifying an additional 23 percent of men who will develop prostate cancer, which would have been missed by previous tools.
A dataset was compiled for the research containing DNA from more than 944,000 men of European, African, Asian and Hispanic ancestry, including more than 150,000 men with prostate cancer.
The 19,391 samples from men with prostate cancer of African descent almost doubled the number of such cases already analyzed in previous studies. This makes the findings crucial in efforts to combat the high rates of prostate cancer in these men, who are twice as likely to develop the disease as their white European counterparts.
The massive genetic analysis was carried out by a global consortium of scientists, led in the UK by researchers from the Institute of Cancer Research in London and generally by the Keck School of Medicine at the University of Southern California in the US, with important contributions. from the US Veterans Health Administration’s Million Veterans Program and Argonne National Laboratory (USA). It was funded by Cancer Research UK, the US National Institutes of Health (NIH) and the Prostate Cancer Foundation.
It also showed that one in six men of African descent is highly genetically susceptible to prostate cancer. By the age of 66, one in six men of African descent will have reached a level of risk not normally seen in men up to the age of 85.
Completing the research puzzle
The findings contribute largely to a research puzzle that is coming together to reveal how genetic and medical information could be used to identify men at highest risk for prostate cancer.
By accurately identifying those who are most at risk, it is hoped that health services can target monitoring to men most likely to develop aggressive disease, for whom early detection and diagnosis would have the greatest impact and potentially save lives. lives.
The UK team at ICR and Royal Marsden NHS Foundation Trust are already taking this further in targeted prostate cancer screening trials, including in men of African descent, funded by Prostate Cancer UK.
The discovery of new genetic variants in men of African descent also opens up avenues of research to discover exactly how these variants increase the risk of prostate cancer, informing risk reduction strategies.
‘A big 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 of black African or Caribbean ancestry, compared to one in eight men of white European ancestry. Using risk stratification will allow us to focus screening efforts on men most likely to have the disease.
“In the past, genetic predisposition studies for prostate cancer have not been representative – with participants of white European ancestry far outnumbering those of other ancestries. You can’t hope to solve a problem like cancer if you just collect a few clues. While there is still work to do to make research truly inclusive and equitable, this study has made huge strides in our ability to find men at higher risk for prostate cancer. I would 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 advance in our ability to more accurately predict prostate cancer risk among men of African and Afro-Caribbean ancestry.
“It’s a great example of team science – only possible through continued collaboration with our international colleagues. We hope our research will play an important role in reducing the health inequalities men face when it comes to prostate cancer – increasing the proportion of prostate cancer cases that are diagnosed early, especially among groups that are currently at greater 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 doctors understand risk in diverse populations. However, more research will be needed to understand whether and how the polygenic risk score could be used in practice to improve how we assess which groups of people may be at higher risk of getting certain types of cancer.”
Christopher Haiman, director of the USC Center for Genetic Epidemiology at the Keck School of Medicine, said:
“We are not going to learn everything there is to know about the genetics of prostate cancer by studying only white men. Increasingly larger studies, involving a broader spectrum of populations, are important if we are to identify genetic markers of risk and develop risk prediction tools that are equally effective in all populations.”
“We will continue to improve this risk score and look for markers that help distinguish aggressive disease from less aggressive disease. Clinical trials will be needed to evaluate the effectiveness of the risk score in helping doctors and patients make decisions about screening.”
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