Sunday 5 July
For the first time, researchers have identified genetic variants commonly found in the population that can increase an individual’s risk of developing glioma, the most prevalent brain tumour. The findings are published today in the journal Nature Genetics.
Scientists at The Institute of Cancer Research in the UK, The University of Texas M.D. Anderson Cancer Center in the US and elsewhere in Europe collaboratively studied the DNA sequences of thousands of people and found five genetic factors that were more common among people who had glioma.
“This is a major discovery,” commented article author and lead researcher Professor Richard Houlston, from the ICR and funded by the Wellcome Trust and Cancer Research UK. “We’ve found the first real evidence that variations in the genes which many people carry can increase their risk of this deadly disease, glioma.”
People who have a relative diagnosed with brain cancer are twice as likely to be diagnosed with a brain tumour themselves. Researchers have previously identified a few rare genetic disorders that increase the risk of brain tumour – but these can only explain a small part of the inherited risk.
Genetic research over recent years has increasingly revealed that most cancers are not triggered by one or two genetic mutations, but instead the involvement of many genetic factors that each slightly increase the risk of cancer.
The scientists theorised that most of the genetic risks of brain tumours were likely due to inheriting several low-risk variants. Professor Houlston and his team compared the DNA of 1,878 glioma patients with 3,670 healthy individuals in the UK and US.
They found five common gene variants which contribute to the risk of people developing brain tumours, and confirmed the results with studies on an additional 2,545 patients and 2,953 controls from Europe.
Importantly, the scientists found that the more of these variants a person has, the higher their risk of developing glioma. People who have eight or more variants are three times more likely to develop glioma than the general population (humans have two copies of DNA, so can have up to ten of these variants).
They believe the five genetic factors found account for between seven and 14 per cent of the inherited risk, and that further research will identify more genetic variants.
“These findings have important implications as glioma is one of the most common tumours in middle-aged people, and the prognosis for sufferers is poor,” ICR Chief Executive Professor Peter Rigby says. “We would also hope that this research could ultimately help scientists develop new treatments that are targeted at patients’ specific molecular defects.”
The genetic variants identified shed new light on how glioma develops, helping scientists home in on new biological targets for treatments. Some of the regions found were associated with genes already linked to cancer development. In descending order of risk, the relevant variants were mapped to the following genes: CCDC26 on chromosome 8, TERT on chromosome 5, CDKN2A on chromosome 9, RTEL1 on chromosome 20 and PHLDB1 on chromosome 11.
“Compared with many other cancers, little is known about the lifestyle or genetic factors that influence the risk of developing brain tumours. This large new study is an important step forward as it unlocks some of the first genetic secrets behind the most common type of brain tumour, glioma,” Dr Lesley Walker, Director of Cancer Information at Cancer Research UK, said.
“Identifying these genetic variants will open up new avenues for scientists to explore, helping them to better understand how gliomas develop, identify who might be most at risk and ultimately find improved ways to diagnose and treat the disease.”
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Note to editors:
- Gliomas account for about 80 per cent of primary malignant brain tumours (cancer that starts in the brain and has not spread from elsewhere), of which about 21,000 people are diagnosed each year in the US
- In the UK, about 4,550 people are diagnosed with brain tumours each year
- Only 14 per cent of people diagnosed with a brain tumour are alive after five years
- CCDC26, on chromosome 8, modulates retinoic acid, which in turn increases programmed cell death in glioblastoma cells and reduces telomerase activity (see next)
- TERT, on chromosome 5, is essential for telomerase activity that preserves telomeres, which are found on the ends of chromosomes and prevent them from unravelling. TERT expression in tumours has been associated with tumour grade and prognosis
- CDKN2A, on chromosome 9, regulates p14, which activates the tumour-suppressor p53. It also regulates cyclin-dependent kinases vital to the cell cycle. At least one copy of the gene is deleted in half of brain tumours, and loss of CDKN2A expression is associated with poor prognosis
- RTEL1, on chromosome 20, maintains genomic stability. Its chromosomal address is amplified in 30 percent of gliomas
- PHLDB1, on chromosome 11, is commonly deleted in neuroblastoma but there is no evidence to date of a role for the gene in glioma
The Institute of Cancer Research
The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting-edge research. In 2009, the ICR marks its 100 years of groundbreaking research into cancer prevention, diagnosis and treatment. Scientists at the ICR have identified more cancer related genes than any other organisation in world. These discoveries are allowing for scientists to develop new cancer treatments. In December 2008, the ICR was ranked as the UK’s leading academic research centre by the Times Higher Education’s Table of Excellence, based on the results of the Higher Education Funding Council’s Research Assessment Exercise. The ICR is a charity that relies on voluntary income. It is one of the world’s most cost-effective major cancer research organisations with more than 95p in every £ directly supporting research. For more information visit www.icr.ac.uk
The Wellcome Trust
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk
Cancer Research UK
- Together with its partners and supporters, Cancer Research UK's vision is to beat cancer
- Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer
- Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients
- Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make
- Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer
- For further information about Cancer Research UK's work or to find out how to support the charity, please visit www.cancerresearchuk.org