According to research published today in the British Journal of Cancer, routine testing for a faulty BRCA2 gene (Kote-Jarai Z et al, BRCA2 is a 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) in men under 65 years with prostate cancer could help identify men who could benefit from new types of targeted treatment.
The study by The Institute of Cancer Research shows that 1 in 100 men who are diagnosed with prostate cancer under the age of 65 have a faulty BRCA2 gene. The researchers said that such men could be prioritized for clinical trials of new targeted therapies like PARP inhibitors.
PARP is short for Poly (ADP-ribose) polymerase. This is an enzyme which helps to repair DNA which has been 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.
PARP inhibitors are already showing considerable promise in trials for cancer linked to BRCA mutations, including breast and ovarian cancers.
According to the study author, Professor Ros Eeles, “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 tumors with BRCA mutations, there may be benefits from routinely testing prostate cancer patients diagnosed before 65 for this gene fault”.
He also pointed out that prostate cancer patients with BRCA2 mutation also tend to have a poorer prognosis so we are also studying whether BRCA2 mutations are more common among patients with more aggressive disease. 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 in the UK under the age of 65 is just below two per cent (around one in 50). For men under-65 with a BRCA2 gene fault this rose to 15 per cent (one in seven).
The researchers have analyzed the 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.
Joel T. Nowak, M.A., M.S.W.