Scientists confirm rare genetic mutations that ramp up bowel cancer risk

Cancer Research UK

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."

ENDS

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References

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

Notes to Editor

About bowel cancer

Around two-thirds of cases are in the large bowel (colon) and the remaining third are in the back passage (rectum).

Bowel cancer screening in the general population

Screening means looking for early signs of a particular disease in ‘healthy’ people who don’t have symptoms, when treatment is more likely to be effective.

In England the NHS Bowel Cancer Screening Programme sends men and women aged between 60 and 69 years a stool testing kit every two years. People aged 70 and over can request a kit. From 2010, people aged 70 to 75 will also be included in the screening programme.

The national bowel screening programme in Scotland started in June 2007. It send men and women aged between 50 and 74 years a stool testing kit ever two years.

In Wales the NHS has started to test people between the ages of 50 and 74 every two years. They currently send out stool testing kits to men and women aged between 60 and 69. It is hoped that the service will roll out to everyone else in the target age group by 2015.

In Northern Ireland the screening programme is expected to be launched in Autumn 2009.

The faecal occult blood (FOB) test works by detecting tiny amounts of blood which cannot normally be seen in bowel movements. Detecting this blood is important as polyps and bowel cancers sometimes bleed. The test is taken at home. The FOB test does not diagnose bowel cancer, but the results will indicate whether further investigation is needed.

Approximately 2 per cent of tests will be positive and further investigation, usually by colonoscopy, will be offered. Most people with a positive test result will not have cancer but the results indicate if further investigation is needed.

** Colonoscopy examines the lining of the bowel wall by using a small flexible camera. It is the most accurate way of diagnosing bowel cancer.