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Bowel cancer gene discovery cracks mystery of families with a strong history of the disease

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by Cancer Research UK | News

23 December 2012

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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 Genetics1.

To find the faults, the researchers from the University of Oxford and The Institute of Cancer Research, London, scanned the genes of 20 people2 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.”

Joe Wiegand, a financial advisor from Hampshire, was diagnosed with bowel cancer seven and a half years ago at just 28 years old. Joe had most of his large bowel removed and six months of chemotherapy. His treatment was successful and he is now followed up once a year with a sigmoidoscopy. As many of Joe’s relatives had also had bowel cancer, during his treatment he was invited to take part in this study to investigate genetic faults that may be behind his cancer.

Joe said: “There’s a very strong history of bowel cancer in my family – my dad’s mother and sister both had it, my dad was diagnosed with it at 43 and a few cousins have had bowel cancers and brain tumours. It’s clear that something’s going on in our family. I hope that taking part in this study will spare my two children the uncertainty of not knowing if they have this gene fault by having a simple yes or no blood test.”

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 the Cancer Research UK press office on 020 3469 8300 or, out-of-hours, the duty press officer on 07050 264 059.

1. Palles, C et al Germline mutations in the proof-reading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas Nature Genetics (2012)