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Last Updated: Aug 19th, 2006 - 22:18:38

Colon Channel
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Latest Research : Cancer : Colon

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New genetic test to spotlight heightened bowel cancer risk
Jul 10, 2006, 20:18, Reviewed by: Dr. Priya Saxena

“This large study has allowed us to develop a new means to identify patient groups who are likely to carry genetic defects responsible for their bowel cancer."

Cancer Research UK scientists have devised a new means to identify groups of people genetically more at risk from bowel cancer. This could lead to new measures to prevent the disease for thousands of people in the future, according to a study published in the New England Journal of Medicine (Wednesday 28 June 2006).

A team at the University of Edinburgh undertook the largest ever study of a particular class of genes – MLH1, MSH2 and MSH6, which when faulty are linked to a minority of all bowel cancers, and devised a new genetic screening method to assess if patients had faults in these genes. Conventional testing of every single patient with bowel cancer would be extremely expensive and not totally accurate.

The current methods of identifying patients with these genetic faults are complex, so the researchers devised a more effective way of detecting them. They tested 870 patients and found 38 of them, or four per cent, had these faults. These genetic errors means that those patients have a higher risk of bowel and some other cancers, and a figure of four per cent is higher that previously reported estimates.

34,900 bowel cancer cases diagnosed in the UK each year and many occur in someone with a family history of the disease. Identifying groups of patients with genetic faults could improve their treatment and survival. However, the discovery will also prove useful for family members who may have inherited these genetic defects – they could, in the future, be monitored to ensure the disease is detected early before symptoms arise.

The large-scale study has been running across Scotland for seven years and has recruited the majority of patients who have developed bowel cancer under the age of 55 years, soon after diagnosis. Over 1300 patients have so far been recruited. Without taking into account prior knowledge of their family history, the researchers studied the patients’ clinical data and took blood and tumour samples to assess them for faults in three of their DNA repair proteins. This approach also allowed the research team to analyse the cancer survival statistics of patients carrying the defective genes and the results emphasise the importance of early detection and prevention.

DNA repair proteins fix damaged strands of DNA, helping to keep the body’s cells under control. However, when damaged DNA can’t be repaired, mutations can occur, causing cells to replicate uncontrollably, and this is a major characteristic of cancer.

Lead researcher Professor Malcolm Dunlop, from the Colon Cancer Genetics Group of University of Edinburgh and the Medical Research Council Human Genetics Unit, said: “This large study has allowed us to develop a new means to identify patient groups who are likely to carry genetic defects responsible for their bowel cancer. The model we developed is easily accessed on our website for clinicians who can then use the prediction to determine who needs genetic blood tests. Our method also shows that a higher proportion of bowel cancer patients fulfilled the criteria for having genetic faults than the current methods would suggest.”

This discovery encouraged the researchers to test their theory on a separate smaller number of patients who were diagnosed at a younger age. This group would further suggest a genetic cause because cancer typically affects older people as they’ve had more time to accumulate genetic damage. A higher number of cases with the faulty genes in the younger group would clearly point to an inherited risk – and that’s what was found. Also, the researchers found that twice as many men as women carried the faults, an intriguing finding that is possibly due to the hormonal differences between the sexes, lifestyle differences or perhaps differences in X and Y chromosomes.

Professor Dunlop added: “In the long term, we hope this study will help identify all bowel cancer patients who carry one of these gene faults and then offer tests to their relatives who have not yet developed cancer, so that preventative measures can be put in place. The findings will also help determine the best treatment for patients with gene faults.”

Professor Timothy O'Shea, University of Edinburgh principle, said: "This research has identified a very useful method that could in future help doctors to rapidly assess whether a newly diagnosed bowel cancer patient carries these genetic faults. Given the significant number of bowel cancer cases in the UK each year, any information which might highlight patients requiring slightly different treatment to prevent their disease from returning is to be welcomed."

Professor Alex Markham, chief executive of Cancer Research UK, said: “These are very valuable findings that will help scientists better understand the process of bowel cancer development, particularly in people who are diagnosed at a young age.

"Identifying people who would benefit from regular examination of the bowel, a colonoscopy, is extremely important - we know that this can prevent the majority of bowel cancers in people who are genetically prone to the disease from developing, because pre-cancerous growths can be detected and removed before they progress to cancer."

- New England Journal of Medicine (Wednesday 28 June 2006)


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