A major new study of >140,000 men has identified 63 new genetic variations that increase the risk of prostate cancer leading researchers to devise a new test to predict which men are most at risk of developing the disease during their lifetime.

Researchers devised a new test combining these single letter genetic variants with more than 100 others previously linked to prostate cancer to predict which men were most at risk of developing the disease during their lifetime. The test identifies 1% of men who are at highest risk because they have inherited many of these risky variants—and they are nearly six times more likely to develop prostate cancer than the population average.

An international team of researchers led by scientists at The Institute of Cancer Research (ICR), London, developed a brand new DNA test to unearth new genetic variants that were particularly hard to find.

Their study is published today in the journal Nature Genetics, and was largely funded by the National Cancer Institute in the US, with additional support from the European Research Council, Cancer Research UK, and Prostate Cancer UK.

Genetic errors in immune pathways

Scientists at the ICR now believe enough is known about prostate cancer genetics to begin assessing whether testing can benefit patients.

They are planning a trial of a DNA test on saliva samples taken in GP practices, to evaluate whether advice or preventative treatment could reduce cases of prostate cancer among those men found to have the highest inherited risk.

The new study used a new DNA analysis—the ‘Oncoarray,’ to compare more than half a million single-letter changes in the DNA code of nearly 80,000 men with prostate cancer and more than 61,000 men without the disease.

The researchers identified 63 new variants in DNA, which when inherited, increased a man’s risk of prostate cancer. Each individually had only a small effect on risk, but the combined effect of inheriting multiple variants could be dramatic.

The 1% of men at highest risk were 5.7 times more likely than the general population to develop prostate cancer—taking the absolute risk from around 1 in 11 to 1 in 2.

And the top 10% in the population risk distribution were 2.7 times more likely to develop the disease than the general population—corresponding to a risk of almost 1 in 4.

Interestingly, the researchers found that many of the new genetic variants were found in the region of genes involved in communication between cells of the immune system and other cells in the body.

This implies that genetic errors in immune pathways may be affecting prostate cancer risk, which could have important implications for potential future treatment of prostate cancers with immunotherapies.

Researchers believe that following the new study, they can now account for almost 30% of a man’s inherited risk of prostate cancer—which may now be enough to start using the information in practical testing strategies.

A readout of inherited prostate cancer risk

Ros Eeles, professor of oncogenetics at the ICR, said:

“By looking at the DNA code of tens of thousands of men in more depth than ever before, we have uncovered vital new information about the genetic factors that can predispose someone to prostate cancer, and, crucially, we have shown that information from more than 150 genetic variants can now be combined to provide a readout of a man’s inherited risk of prostate cancer.”

“If we can tell from testing DNA how likely it is that a man will develop prostate cancer, the next step is to see if we can use that information to help prevent the disease.”

“We now hope to begin a small study in GP practices to establish whether genetic testing using a simple spit test could select high-risk men who might benefit from interventions to identify the disease earlier or even reduce their risk.”

Professor Paul Workman, Chief Executive of the ICR, said:

“We have seen dramatic progress in recent years in our understanding of the genetics of prostate cancer, and this new research is another big step forward that tells us more about why some men develop the disease and others don’t.”

“We are on the cusp of moving from theory to practice—from explaining how genetics affects prostate cancer risk, to testing for genetic risk and attempting to prevent the disease.”

“This study also gives us important information about the causes of prostate cancer and the potential role of the immune system, which could ultimately be employed in the design of new treatments.”