Scientists show men most at risk of life-threatening prostate cancer can now be identified by mutations in their DNA and be monitored for life
A collection of 13 gene defects can be used to identify men most at risk from life-threatening prostate cancer, scientists have shown.
The discovery raises the prospect of screening men for the first time to single out those predisposed to developing aggressive and potentially deadly tumours.
Scientists tested blood samples from 191 British men with prostate cancer who had at least three relatives affected by the disease.
Fourteen carried “loss of function” mutations in their DNA that completely stopped a gene working. Having any one of these flaws dramatically boosted the chances of developing invasive, spreading prostate cancer.
In future, men could be tested for the variants in the same way that women are currently screenedfor breast cancer genes, the researchers believe. This would herald a revolution in prostate cancer diagnosis and treatment.
Professor Ros Eeles, from London’s Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust, said: “Our study shows the potential benefit of putting prostate cancer on a par with cancers such as breast cancer when it comes to genetic testing.
“Although ours was a small, first-stage study, we proved that testing for known cancer mutations can pick out men who are destined to have a more aggressive form of prostate cancer.
“We already have the technical capabilities to assess men for multiple mutations at once, so all that remains is for us to do further work to prove that picking up dangerous mutations early can save lives.
“If so, then in the future, genetic testing may be needed as part of the prostate cancer care pathway.”
Women with a strong family history of breast cancer are routinely tested for BRCA1 and BRCA2 gene defects, both of which greatly increase their chances of developing the disease.
But the picture is much more complicated for prostate cancer, which seems to be linked to a multiplicity of different genetic mutations. Currently there is no way of screening men who might be at risk from ferocious ‘tiger’ prostate cancers that could cut short their lives.
Many diagnosed prostate cancers, known as ‘pussycats’, are slow-growing and can safely be left untreated while their progress is monitored.
An effective screening test would make it possible to step in early and treat men with developing dangerous cancers before they progress too far.
Despite big advances in treatment in the last 10 to 20 years, around 11,000 of the 40,000 men diagnosed with prostate cancer each year in the UK die from the disease.
Currently there is no way of screening men who might be at risk from ferocious ‘tiger’ prostate cancers that could cut short their lives
The ICR scientists used cutting-edge DNA sequencing technology to assess 22 known cancer genes at the same time.
Each of the 14 carriers had a mutation affecting one of eight DNA repair genes – genes whose job is to fix damage to DNA that can lead to cancer.
Two men had the same mutation in the BRIP1 gene. The others all had different variants, some of which shared the same genes. All were serious enough to shut a gene down and prevent it producing a working protein.
Among the affected genes were BRCA1 and BRCA2, variant forms of which are implicated in both breast and ovarian cancer. Four of the mutations were identified in the BRCA2 gene. The other genes were ATM, CHEK2, BRIP1, MUTYH, PALB2 and PMS2.
Among the study participants, men with one of the mutations were found to be 13 times more at risk of having high-grade T4 tumours or cancer that had spread to the lymph nodes or travelled beyond the prostate gland to other organs.
Both carriers of the mutations and non-carriers were typically diagnosed at around the age of 59, and no significant association was seen with levels of PSA (prostate specific antigen), the most widely used blood marker for prostate cancer.
Nor was a high Gleason score, an aggressiveness rating obtained by examining biopsy tumour samples, more common in men with the gene variants.
The findings are reported in the latest edition of the British Journal of Cancer.
Co-author Zsofia Kote-Jarai, from the Institute of Cancer Research, said: “One of the important messages to come out of our study is that mutations to at least eight genes – and probably many more – greatly increase the risk of aggressive prostate cancer.
“Any future screening programme would need to assess as many of these genes as possible – more than we currently look for in women at risk of breast cancer, for example.”
Iain Frame, director of research at the charity Prostate Cancer UK, which part-funded the study, said: “The minefield of prostate cancer diagnosis is one of the biggest hurdles facing treatment of the disease today.
“Current tests fail to differentiate between aggressive cancers that could go on to kill, and cancers that may never cause any harm. This lack of clarity means that too often men and their doctors are left having to make incredibly difficult decisions on whether to treat the disease or not. We urgently need to understand more about which men are at risk of developing prostate cancer and in particular aggressive forms of the disease.
“Genetic testing to predict risk could revolutionise how we treat the 40,000 men diagnosed with the disease every year in the UK. These results are exciting as they add to the growing weight of evidence that men with a family history of prostate cancer who possess certain genes may be at higher risk, providing us with another crucial piece of the jigsaw.”