23 December, 2012
Cancer Research UK-funded scientists have discovered that two gene faults increase the risk of bowel cancer in families with a strong history of developing the disease, who, until now, had no explanation as to why their risk was greater. The research is published in Nature Genetics today, Sunday*.
To find the faults, the researchers from the University of Oxford and The Institute of Cancer Research, London, scanned the genes of 20 people** from families with a strong history of bowel cancer. They found everyone who had a faulty POLE or POLD1 gene developed bowel cancer or had a precancerous growth in the bowel.
The two genes are so-called ‘dominant’ genes, where only one faulty copy needs to be inherited for someone to be at a high risk of developing bowel cancer.
To confirm their findings they then looked for the faults in almost 4,000 people with bowel cancer and 6,700 without the disease. Neither of the faults were found in people without bowel cancer, while 12 people with the POLE gene were found in the bowel cancer group and one person had a POLD1 gene fault.
The POLD1 fault was also found to increase the risk of getting womb cancer and possibly brain tumours with seven people in the study being diagnosed with womb cancer and one developing two brain tumours.
Cancer Research UK’s Professor Ian Tomlinson, lead researcher based at the University of Oxford, said: “There are some families where large numbers of relatives develop bowel cancer but who don’t have any of the known gene faults that raise the risk of developing the disease.
“These two faults are rare, but if you inherit them your chance of bowel cancer is high. By testing people with a strong family history of the disease for these faults, we can identify those who are at high risk and try to prevent the disease by using colonoscopy and other methods.”
POLE and POLD1 are involved in scanning and repairing damage to DNA, removing incorrect sequences from the DNA chain. Without these genes, affected individuals build up damage in their DNA which can cause bowel cancer.
Study co-leader Professor Richard Houlston from The Institute of Cancer Research said: “Uncovering gene faults like these two is extremely important, as inherited susceptibility plays a role in the development of about a third of all cases of colorectal cancer.
“This is one of the most important discoveries in bowel cancer genetics in years. It should allow us to manage families affected by inherited bowel cancer much more effectively, and it offers new clues for the prevention or treatment of all forms of the disease.”
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “This research provides another piece of the puzzle for families who have a much greater risk of developing bowel cancer.
“Cancer Research UK scientists have played an important role in finding the gene faults that increase cancer risk. Their work means doctors can help families with a strong family history by preventing cancer from developing or diagnosing it earlier to help more people survive.”
For media enquiries please contact Simon Shears in the Cancer Research UK press office on 020 3469 8054 or, out-of-hours, the duty press officer on 07050 264 059.
Notes to editors
*Palles, C et al Germline mutations in the proof-reading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas Nature Genetics (2012)
** Eight of the 20 people had developed bowel cancer, while the rest had a first degree relative who had developed the disease.
Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school.
From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.
A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.
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 www.icr.ac.uk
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