New Panel of Genes Identifies Men at Highest Risk of Aggressive Prostate Cancer

A new panel of genes could pick out men at highest risk of developing prostate cancer and pick out those already diagnosed who are likely to have particularly aggressive forms of the disease, a large-scale genetic analysis has found.

The panel could be developed into a test for use in screening services so that high-risk men could be closely monitored, increasing the chance of catching the disease early.

And as the test looks at inherited prostate cancer risk, family members of men at high risk could in future also consider getting tested.

In men already diagnosed with prostate cancer, the gene panel could help pick out patients with more aggressive disease, who could be offered different treatment options most likely to work for them.

New genes linked to prostate cancer risk and aggressiveness

Scientists at The Institute of Cancer Research, London, analysed the genes of more than 1,200 men with young-onset prostate cancer – in which inheritance is likely to play a particularly important role – and more than 1,100 healthy men.

The researchers analysed the effect of small variations in 175 DNA repair genes. On their own most of these genetic changes have only a minor effect, but together they can add up to an increased risk of prostate cancer.

They identified 23 genes in total, in which inherited changes were associated with an increased risk of prostate cancer, others with aggressive disease, and some with both.

Only six of the genes identified in the study had been previously identified as prostate cancer risk genes – with 17 genes newly linked to prostate cancer risk and aggressiveness.

The study is published in the journal European Urology, and was funded by Cancer Research UK and Prostate Cancer UK.

Link with aggressive disease

The team at the ICR found that changes in 18 of the DNA repair genes were more than three times as common in men with prostate cancer than in healthy men – with 9 per cent of prostate cancer patients having at least one change, compared with 3 per cent of healthy men.

The link with aggressive disease was even stronger, with gene changes found in 8 per cent of men with aggressive prostate cancer compared with less than 1 per cent in other patients – an 11-fold difference.

The four aggressive disease genes also affected survival, with only 60 per cent of men with changes in these genes living for five years or more, compared with 91 per cent of healthy controls.

Largest study of its kind

The new study is the largest of its kind, both analysing all known DNA repair genes, and including a comparison with healthy men to determine the effect of gene changes on prostate cancer risk.

The large scale of the study was essential for identifying the new genes, as each single gene change occurs in a small number of people and plays a small role in prostate cancer risk.

Next, studies looking at different groups of patients are needed to confirm the effect of the genes on cancer risk, their link with aggressive disease and the effect on survival rate.

Professor Ros Eeles, Professor of Oncogenetics at the ICR, said:

“Our study looked at a large number of DNA repair genes in prostate cancer. We have identified 17 new prostate cancer risk genes, some of which raise the risk of developing the disease, and others of which increase the likelihood that it will be particularly aggressive.

“In future, healthy men could be offered saliva or blood tests in GP surgeries, to test their risk of developing prostate cancer based on a panel of genes including those found in this study. Doctors could offer high-risk men more frequent screening services, and when we have more research about the risks of these genetic mutations, we may be able to test other family members also.

“Testing for genes linked with aggressive prostate cancer could be especially helpful for informing treatment decisions in men already diagnosed with the disease. At the moment, men can receive a diagnosis of prostate cancer without really knowing how the disease is likely to affect them, but in future a test could pick out those who are likely to develop aggressive disease and need intensive treatment.”

This article has been republished from materials provided by Institute of Cancer Research. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Daniel A. Leongamornlert, et al. Germline DNA Repair Gene Mutations in Young-onset Prostate Cancer Cases in the UK: Evidence for a More Extensive Genetic Panel. European Urology (2019) DOI: https://doi.org/10.1016/j.eururo.2019.01.050