New research published in the British Journal of Cancer shows that routinely testing for a faulty BRCA2 gene in men under the age of 65 years with prostate cancer could help identify men who could benefit from new types of targeted treatment.

Approximately 9,500 men under the age of 65 years are yearly diagnosed with prostate cancer, with around a quarter of all cases in the UK. One of the largest risk factors for prostate cancer is age. Although prostate cancer is quite rare in men aged 50 years or younger, more than half of all cases are diagnosed in men over the age of 70 years. The study led by The Institute of Cancer Research with funding provided by Cancer Research UK and Prostate Action reveals that one in 100 men who are diagnosed with prostate cancer under the age of 65 has a faulty BRCA2 gene.

According to the researchers these patients could be prioritized for clinical trials of new targeted therapies like PARP inhibitors, which have already shown substantial promising results in patient trials for cancer associated with BRCAmutations, including some breast and ovarian cancers.

PARP is a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death. PARP inhibitors block this process. Cancer cells have damaged DNA that cannot be repaired in the usual process as PARP inhibitors prevent the repair process causing tumors to either stop growing or shrink.

Professor Ros Eeles from The Institute of Cancer Research and author of the study commented:

“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 BRCAmutations, 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 researches decided to establish whether the faulty BRCA2 gene was associated with the development of prostate cancer at a young age. They examined blood samples of nearly 2,000 men with prostate cancer for their entire genetic code of the BRCA2 gene.

The researchers discovered that more than 1%, i.e. one in a hundred men with prostate cancer had a faulty BRCA2 gene, all of which were diagnosed in men under the age of 65 years which indicates that this BRCA2 gene mutation could be a major key-stone in prostate cancer in younger man.

A mutated BRCA2 gene was associated with an eight-times higher risk of prostate cancer by men aged 65 years. The risk of a man developing prostate cancer below the age of 65 years is just under 2%, i.e. around one in 50 men. For men below the age of 65 years with a BCRA2 gene mutation the risk increased by 15%, i.e. one in seven.

Dr Lesley Walker, director of cancer information at Cancer Research UK, commented:

“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.”

Chief executive of Prostate Action, Emma Malcolm added:

“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.”

Written by Petra Rattue