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Scientists confirm rare genetic mutations that ramp up bowel cancer risk

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by Cancer Research UK | News

1 October 2009

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CANCER RESEARCH UK funded scientists have found that people who carry rare mutations within both copies of a gene called MUTYH are 28 times more likely to develop bowel cancer compared to the general population, according to a study in the Journal of Clinical Oncology*.

The scientists, at The Institute of Cancer Research (ICR), replicated previous findings that showed this increase in risk only exists if mutations are in both copies (called biallelic mutations) of the gene. The research also adds important insights into the controversy surrounding whether or not having just one mutation (or monoallelic mutation) does raise an individual’s risk of bowel cancer.

In the largest study of its kind, they conclusively found that carriers of mutations in only one copy have no significant increase in risk for bowel cancer compared to that of the general population. They were able to demonstrate this by combining data from this study and other studies. In total they looked at the genetic makeup of more than 30,000 people.

The researchers looked for two mutations in the MUTYH gene, called Y179C and G396D, in over 9,000 bowel cancer patients and over 5,000 healthy individuals. The MUTYH gene codes for a DNA base excision repair protein which removes mistakes that build up in the DNA sequence.

They observed that all 27 people who carried biallelic mutations were in the bowel cancer group, and they accounted for 0.3 per cent of all bowel cancers in this study. They also found that these patients developed bowel cancer when they were relatively young – in their 50s. Most bowel cancers, over 80 per cent, occur in people aged 60 and over.

Although the contribution of biallelic mutations to the overall incidence of bowel cancer is not high, the risk of developing the disease is substantial.

Because of this young age and high risk for developing bowel cancer the researchers recommend that siblings of biallelic mutation carriers should have annual colonoscopy** from as early as 20 years of age as they have a 25 per cent chance of also having the two genetic mutations.

Study author Steven Lubbe, a PhD student at the ICR, said: “Our research shows for the first time the increased risk of developing bowel cancer that carriers of these mutations have, but interestingly it does not apply to people who only carry one damaged copy of the gene. Although mutations in this gene are very rare and it will only be relevant to a very small percentage of the overall cases of bowel cancer, the results here could be used to detect those people with some of the highest risks and help target screening to relatives of known carriers.”

Bowel cancer is the third most common cancer in the UK. Each year more than 37,000 people are diagnosed in the UK, that’s more than 100 people a day. Around 16,000 people a year die from bowel cancer in the UK.

Senior author Professor Richard Houlston, head of the ICR’s Molecular and Population Genetics Team and Steven Lubbe’s supervisor, said: “This important step forward in the search for bowel cancer genes is all the more impressive having been carried out by a PhD student, showing the value in the ICR and Cancer Research UK’s focus on fostering young scientific talent.”

Cancer Research UK’s director of cancer information, Dr Lesley Walker, said: “This interesting study adds to our understanding of the inherited risk of bowel cancer. Research such as this could help us to identify those who are most at risk of cancer so we can target measures that prevent the cancer or detect it early so treatment is targeted at those with the greatest need.”


For media enquiries please contact the Cancer Research UK press office on 020 7061 8300 or, out-of-hours, the duty press officer on 07050 264 059.

Lubbe SJ, Di Bernardo MC, Chandler IP, & Houlston RS (2009). Clinical implications of the colorectal cancer risk associated with MUTYH mutation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 27 (24), 3975-80 PMID: 19620482