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Malcolm Dunlop

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The genetic causes of bowel cancer

University of Edinburgh
Institute of Genetics and Molecular Medicine
MRC Human Genetics Unit
Western General Hospital
Edinburgh
EH4 2XU

Professor Malcolm Dunlop is leading research into the genetic and environmental causes of bowel cancer at the MRC Human Genetics Unit in Edinburgh. Bowel cancer is the UK's third most common cancer and Scotland itself has one of the highest rates of this disease in the world.

A substantial proportion of people who develop bowel cancer have inherited faults in genes that predispose them to the disease. If we can identify people at increased risk, then they could be referred to specialists for regular screening and prevention advice.

Searching for inherited high-risk bowel cancer genes

One area of Professor Dunlop's work is focusing on gene defects that give a high risk of bowel cancer. In particular, he is studying an important set of genes known as the DNA mismatch repair (MMR) genes. These help repair tiny faults in our DNA that can lead to cancer.

People who inherit a faulty MMR gene from one or both parents have a higher risk of developing cancers of the womb, ovaries and stomach as well as bowel cancer. And they often develop cancer at an earlier age than the general population.

Scientists estimate that there are around 15,000 people in the UK with MMR gene faults, including around 1,500 people in Scotland. Professor Dunlop's group has screened all Scottish bowel cancer patients diagnosed before the age of 55 for faults in MMR genes as well as other genes thought to be linked to bowel cancer.

Using this information, he has been able to develop a reliable test to predict the presence of MMR gene faults in groups of people with bowel cancer. This test can be used by doctors to guide treatment decisions and to identify relatives who may also have inherited the faulty genes and be at increased risk of disease.

Searching for inherited low-risk bowel cancer genes

Several gene variations that are common in the general population are associated with a small but significant increase in bowel cancer risk. Because these changes are common and individuals may have several of them, scientists believe that the overall contribution to bowel cancer rates in the population is very important.

Professor Dunlop has already identified a number of these gene changes. The long term aim is to use this information to develop tests that can predict an individual's risk of bowel cancer. It is likely to be quite a while before such tests could be applied on a large scale, but Professor Dunlop believes it will be possible.

Bowel cancer prevention

The team is also exploring ways to prevent bowel cancer. Their laboratory-based studies are looking at the use of aspirin-like drugs known as NSAIDs, and seeing whether these can reduce bowel cancer risk in people who are more likely to develop this disease.

Professor Dunlop and his team aim to define the role of defects in DNA mismatch repair genes in colorectal cancer susceptibility and to investigate the consequences of defective mismatch repair in tumours and in normal somatic tissue.

Other research projects by Malcolm Dunlop

Science Committee Programme
Funding period: 01 January 2011 to 31 December 2015