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27
Mar
2013

Coordinating a global hunt to track down the genes responsible for prostate cancer risk

For Professor Ros Eeles, her world-leading work in prostate cancer genetics is about much more than the thrill of scientific discovery. As not only a researcher but a practicing doctor, she is fired by a desire to turn the once theoretical world of cancer genetics into practical advances that have real benefits for patients.

Professor Ros Eeles
Professor Ros Eeles
“Working with a dedicated team of doctors, nurses, research assistants and scientists, with all of us having the common goal of unearthing answers to problems is one of the most rewarding aspects of the research process.”

 

Ros Eeles, Professor of Oncogenetics at the Institute of Cancer Research (ICR) and Honorary Consultant in Clinical Oncology at The Royal Marsden NHS Foundation Trust, is in hot pursuit of the genetic variants that increase men’s risk of prostate cancer – convinced that knowledge she is rapidly accumulating will eventually provide the basis for targeted screening programmes for the disease.

“I have a passion for solving problems and helping patients, so this led me naturally to a career in medicine,” Professor Eeles explains. "I chose to specialise in cancer genetics, as this a very exciting branch of medicine and it provides real promise. We can test a patient’s DNA and tailor a treatment according to their specific genetic variants, and we can take measures to prevent disease. Here at the ICR, we are in a fantastic position to take the basic research findings out of the laboratory and use this knowledge to improve patient outcome in the clinic.”

Searching for the genes that increase a man’s possibility of developing prostate cancer is a hugely daunting task – but Professor Eeles has been rallying together researchers all across the world to help her with this task.

Years of hard work is coming to fruition with a flurry of papers on prostate cancer risk being published in a range of prestigious journals this week surrounding the Collaborative Oncological Gene-environment Study (COGs) study. Research led by scientists at the ICR and the University of Cambridge, and funded by Cancer Research UK and the Wellcome Trust, found over 80 regions of the genome that can increase an individuals risk of breast, prostate and ovarian cancers. Professor Ros Eeles contributes to the findings of prostate cancer risk, where 23 genetic variations were revealed, taking the discovered total to 78. Importantly, 16 are linked with the more aggressive and life-threatening forms of the disease. “These results allow us, for the first time, to identify men who have a very high risk of developing prostate cancer during their lifetime through inheritance of multiple risk genetic variants. If we can show from further studies that such men benefit from regular screening, we could have a big impact on the number of people dying from the disease, which is still far too high.”

Samples used for the COGs study were taken from PRACTICAL, an international consortium set up by Professor Eeles, which helps scientists find and evaluate potential prostate cancer risk genes. Researchers across the globe deposit DNA from prostate cancer patients into a communal bank, allowing scientists access to a huge resource of genetic samples. By comparing the genetic make-up of cancer cases with healthy individuals, researchers can make a reliable assessment of the risk associated with these genes. “With 34 groups participating and 56,000 blood samples available, PRACTICAL is becoming an invaluable resource,” Professor Eeles states. “So far, an incredible 50 out of 78 genetic variants known to be associated with prostate cancer have been found by this initiative.”

Mutations in the BRCA1 and BRCA2 genes are not common in the population, but men who have alterations in these genes have an increased risk of prostate cancer, and are more likely to have a fast-growing form of disease than those who do not carry the mutation. The IMPACT study is looking into whether regular screening of men who have mutations in theirBRCA1 or BRCA2 genes would lead to earlier diagnosis of aggressive prostate cancers. Nearly 2,000 men will be screened for at least five years, and an initial analysis of 300 men has already revealed some fascinating findings. “Early results show men who have the BRCA1 or BRCA2mutations are more likely to develop an aggressive form of prostate cancer compared with the findings from the general population screening, where over half of the prostate cancer cases might never need treatment and are not aggressive,” Professor Eeles explains. “Targeting men who carry theBRCA1 or BRCA2 alterations could lead to an earlier diagnosis and improved survival.”

“Ultimately, it’s the patients who motivate me in my work, and knowing that our research is impacting patient care is truly inspiring.”

 

Previous research suggests that if a man has a family history of prostate cancer, he will be at an increased risk of developing this disease. We are trying to find out the science behind this through The UK Genetic Prostate Cancer Study (UKGPCS).

Led by Professor Eeles, this is the largest prostate cancer study of its kind in the UK and it’s seeking to increase our understanding of the genetic causes behind prostate cancer. “We already know about BRCA1 orBRCA2, so we are looking at other faulty genes that increase a man’s risk of developing prostate cancer,” Professor Eeles explains. “If we can find these specific alterations, we can screen other family members to see if they are also at a higher risk of developing prostate cancer. Once we have these insights, we can go on to develop new prostate cancer treatments and prevention strategies for the future.”

So what about our existing knowledge of prostate cancer genetics? Can existing genetic tests and family history profiling be used to find men at higher risk of prostate cancer, so they can be targeted for screening? Professor Eeles and her researchers hope that the PROFILE study can answer these questions. “Screening men at higher risk could potentially lead to earlier diagnoses, which would improve their chances of cure,” Professor Eeles says. “We are looking at ways to optimise screening of such men, using magnetic imaging of the prostate, where we can visualise the internal structure of the prostate, and through prostate sampling use biopsies to determine if there are any changes to the cells that would indicate cancer. The ultimate goal is to eventually develop a genetic profiling test for the general population that can be used in an accessible and effective prostate screening programme.”

One of the major stumbling blocks in treating prostate cancer is determining who needs aggressive treatment – some are slow growing and will never need treatment whilst others will develop quickly. Researchers collaborating around the world are beginning to pinpoint the genes that put men at higher risk, and can begin to target treatment to those patients while potentially sparing thousands of others unnecessary therapy. The second hurdle researchers’ face is that the more aggressive prostate cancers can become resistant to current treatments. Knowing the genetic make-up of those prostate cancers will help doctors take a targeted approach to developing new treatments for these cancers that would otherwise kill the patient.

For Professor Eeles, advances like that are proof that cancer genetics not only provides a fascinating insight into the causes of cancer – but a clear signal of how best to defeat it.

“Ultimately, it’s the patients who motivate me in my work, and knowing that our research is impacting patient care is truly inspiring.”

Tags

prostate cancer UK Genetic Prostate Cancer Study
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