Screening men with a family history of prostate cancer for a range of gene mutations can identify those who are at high risk of aggressive forms of the disease and in need of lifelong monitoring, a new study has shown.
Scientists at The Institute of Cancer Research, London, found screening of men who had multiple relatives with prostate cancer was able to pick up 14 mutations in known cancer genes that predicted the development of the disease.
The research was mainly funded by Prostate Cancer UK with additional support from Cancer Research UK, and is published in the British Journal of Cancer today (Friday).
The findings are important because they demonstrate not only that some men have a genetic profile that puts them at higher risk of prostate cancer, but that particular genetic profiles match to a higher risk of advanced, invasive disease. A big challenge facing prostate cancer researchers is to find ways of predicting which men will have life-threatening forms of the disease, to allow treatment to be tailored more effectively.
Scientists at The Institute of Cancer Research (ICR) analysed blood samples from 191 men with prostate cancer at several different UK centres. They were able to use new 'second generation' DNA sequencing technologies to assess mutations in 22 different known cancer genes at once – opening up for the first time the prospect of rapid genetic screening for prostate cancer for a wide range of mutations.
The researchers looked at men with a history of three or more cases of prostate cancer in their close family, in order to mirror use of family history as a criterion for existing gene testing programmes in breast cancer.
The researchers found 13 'loss of function' mutations – which prevent the genes from producing a properly working protein – in eight DNA repair genes. The genes tested for were BRCA1 and BRCA2, which are already routinely tested for in women with a strong family history of breast or ovarian cancer, plus ATM, CHEK2, BRIP1, MUTYH, PALB2 and PMS2.
Men with any of these 13 mutations were much more likely than those without to develop an advanced, invasive form of cancer which spread to the lymph nodes or other parts of the body, and to die from the disease.
Study co-leader Professor Ros Eeles, Professor of Oncogenics at The Institute of Cancer Research, London, and Honorary Consultant at 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."
Fellow study co-leader Dr Zsofia Kote-Jarai, Senior Staff Scientist at The Institute of Cancer Research, London, 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."
Dr Iain Frame, Director of Research at Prostate Cancer UK, 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."
Notes to Editors
For more information contact the ICR press office on 020 7153 5312 / henry.french@icr.ac.uk. For enquiries out of hours, please call 07976 751984.
The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden Hospital and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk
About Prostate Cancer UK
Prostate Cancer UK fights to help more men survive prostate cancer and enjoy a better quality of life. We support men and provide vital information. We find answers by funding research into causes and treatments. And we lead change, raising the profile of the disease and improving care. We believe that men deserve better.
Prostate cancer is the most common cancer diagnosed in men in the UK. Over 40,000 men are diagnosed with prostate cancer every year. Every hour 1 man dies from prostate cancer. One in four Black men will develop prostate cancer at some point in their lives.
Anyone with concerns about prostate cancer can call Prostate Cancer UK's confidential Helpline on 0800 074 8383 or visit http://www.prostatecanceruk.org. The helpline is free to landlines, staffed by specialist nurses, and open from 9am to 6pm Monday to Friday with late opening until 8pm on Wednesdays.
About Cancer Research UK
- Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research
- The charity's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
- Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every pound donated.
- Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.
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About the British Journal of Cancer (BJC)
The BJC is owned by Cancer Research UK. Its mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence and consistent high standards have made BJC one of the world's premier general cancer journals. http://www.bjcancer.com
Journal
British Journal of Cancer