Gene testing young prostate cancer patients could help target treatment

British Journal of Cancer

ROUTINELY testing for a faulty BRCA2 gene in under-65s with prostate cancer could help identify men who could benefit from new types of targeted treatment, new research published in the British Journal of Cancer* today shows.

The study, funded by Cancer Research UK and Prostate Action and led by The Institute of Cancer Research, shows that one in 100 men who are diagnosed with prostate cancer under the age of 65 has a faulty BRCA2 gene.

The researchers said that such patients could be prioritised for clinical trials of new targeted therapies like PARP inhibitors.

PARP inhibitors are already showing considerable promise in patient trials for cancer linked to BRCA mutations, which includes some breast and ovarian cancers.

PARP inhibitors block PARP, a protein which helps repair damaged DNA. Cancer cells have damaged DNA and rely on PARP to repair it but PARP inhibitors helps to stop this from happening – so tumours either stop growing or shrink.

Study author Professor Ros Eeles from The Institute of Cancer Research said: “Our study shows that men diagnosed with prostate cancer at a young age have a higher chance of carrying a faulty BRCA2 gene.

“With the arrival of PARP inhibiting drugs to target tumours with BRCA mutations, there may be benefits from routinely testing prostate cancer patients diagnosed before 65 for this gene fault.

“Prostate cancer patients with this gene fault also tend to have a poorer prognosis so we are also studying whether BRCA2 mutations are more common among patients with more aggressive disease.

“Ultimately, we hope to develop a full clinical picture of BRCA2-linked cancers, which will help us to work out the best way to treat these patients.”

The researchers analysed the entire genetic code of the BRCA2 gene in blood samples of almost 2,000 men with prostate cancer.

They hoped to find out whether this faulty gene was linked to developing prostate cancer at a young age.
Age is the biggest risk factor for prostate cancer – more than half of all cases of the disease are diagnosed in men over 70. It is quite rare in men under 50.

Around 9,500 men under-65 are diagnosed with prostate cancer each year – about a quarter of all cases in the UK.
The results showed that over one per cent of men in the study (1 in 100) with prostate cancer had a faulty BRCA2 gene.

All these BRCA2 genetic mutations were in men diagnosed under-65, which suggests that this finding is important in prostate cancer cases in younger men.

A faulty BRCA2 gene was linked to an eight-fold increased risk of prostate cancer by the age of 65.

The risk of a man getting prostate cancer under the age of 65 is just below two per cent (around one in 50). For men under-65 with a BCRA2 gene fault this rose to 15 per cent (one in seven).

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “Once gene testing becomes faster and cheaper, this study suggests that a new range of treatments could potentially open up for some prostate cancer patients.

“Cancer Research UK has funded researchers across the country, including those at the ICR, to develop drugs like PARP inhibitors which target breast and ovarian cancers caused by specific faulty genes.

“It would be great if we could use these drugs to treat prostate cancer as well.”

Emma Malcolm, chief executive of Prostate Action, said: “One of the biggest single issues in prostate cancer lies in developing more accurate diagnostics so that men can be treated more effectively, especially identifying those men that are at a higher risk of developing the disease. This discovery of increased prostate cancer risk in men with a mutation in the BRCA2 gene may lead to more treatment options for men in the future.”

ENDS

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References

*Kote-Jarai Z et al, BRCA2 is a moderate penetrance gene contributing to young onset prostate cancer: implications for genetic testing in prostate cancer patients British Journal of Cancer (2011) doi:10.1038/bjc.2011.383

Notes to Editor

PARP is short for Poly (ADP-ribose) polymerase. This is an enzyme which helps to repair DNA which is damaged. PARP inhibitors block PARP and prevent mistakes being passed on to daughter cells when cells grow and divide. The PARP repair kit alone isn't fully effective so mistakes are replicated when the cell divides and grows - leading to cancer. But, by blocking PARP the cell is no longer able to 'muddle on' - it can no longer repair any damage. The cell cannot replicate and it dies.

Healthy cells are unaffected if PARP is blocked because they either contain one or two working BRCA genes which do an effective repair job.

BRCA2 is a gene that increases the risk of getting breast and ovarian cancer in women and breast and prostate cancer in men.