Research published today has discovered a far higher proportion of inherited DNA mutations in men with advanced prostate cancer than previously suspected, opening up new possibilities for targeted treatments.

7 Jul 2016

Scientists have known for a while that around five per cent of men with prostate cancer (of any form) inherit mutations in the genes responsible for repairing damaged DNA from their parents. But now, according to results published in the New England Journal of Medicine today, it looks like that percentage increases to over 11 per cent in men with advanced forms of the disease. 

Mutations in DNA damage repair genes like BRCA1 or BRCA2 – which are the most well known, but there are many more – mean that cells can’t repair broken DNA as efficiently as usual. This leads to mistakes building up in the DNA code. In some cases, this may cause the cell to die. But in others, it may instead become cancerous. That's why people with mutations in these genes are at higher risk of certain types of cancer like breast, ovarian or prostate cancer.

In contrast to the five percent of all men with prostate cancer, 11.8 per cent of men with advanced prostate cancer had an inherited mutation

In this new study – which was part-funded by us through the London Movember Center of Excellence and a Fellowship awarded to Dr Joaquin Mateo – researchers looked at the DNA in saliva, blood cells or non-cancerous tissue (so that they knew they were looking at inherited DNA, not cancer-related DNA changes) in men with advanced prostate cancer. They didn’t ask these men whether they had a history of cancer in their family, but just tested them for mutations in known DNA damage repair genes.

They found that, in contrast to the five percent of inherited DNA damage repair mutations in all men with prostate cancer (including localised disease), 11.8 per cent of men with advanced prostate cancer had an inherited mutation.

This study has important implications for treating men with advanced prostate cancer, because men with these mutations are more likely to do better on certain types of treatment. It also has implications for the families of men with advanced prostate cancer and their own risk of developing the disease.

The percentage of all men with prostate cancer who have an inherited DNA damage repair mutation (five per cent) is too low to recommend routine testing for these genetic changes. But these results suggest that, regardless of family history, men with advanced prostate cancer should be tested for inherited DNA damage repair mutations as it could improve their chances of getting the right treatment.

This research suggests it might be beneficial to test all men with advanced prostate cancer for changes in these genes to help decide which treatments to give them

There is, though, still a lot of work to do to see how this testing could be done in a routine clinical setting, and to consider the consequences for men and their families. At the moment, BRCA1 and BRCA2 are the only two genes that can be tested for on the NHS, and it is only offered to men with a very strong family history of prostate, breast or ovarian cancer. It will take longer for a test that can cover the full panel of genes used in the research paper to become available and recommended for wider use.

Dr Iain Frame, our Director of Research, said: "A huge current focus for prostate cancer research is how to target the right treatments to the right patients for best effect. We already know that men with prostate cancer who have a mutation of a certain family of inherited genes (such as BRCA1 and BRCA2) respond better than other patients to treatments like olaparib. The findings of this trial show for the first time that around 11.8 per cent of men with advanced prostate cancer have, in fact, inherited one of these genetic mutations.

"This research suggests that in the future it might be beneficial to test all men with advanced prostate cancer for changes in these genes, in order to help decide which treatments to give them."

Read more about genetic testing in our interview with Sarah Rose, a genetic counsellor at Guy’s and St Thomas’ NHS Trust.

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