Bowel cancer genes that triple risk discovered

Dec 17 2007

Cancer Research UK funded scientists have identified two common genetic variants that could triple a person's risk of getting bowel cancer. Their findings are published in Nature Genetics (Sunday).

Earlier this year, Cancer Research UK funded scientists found the first genetic region commonly associated with bowel cancer risk when they undertook a search of the human genome. The paper published today and another paper published last month identify two areas near specific genes that strongly influence bowel cancer risk.

The researchers estimate that up to a third of all bowel cancers may be associated with these newly identified, high-risk variants of the genes - about 12,000 cases per year in the UK. The increased risk of bowel cancer when these two genes are present is small, but if both these and two other high-risk genetic variants identified earlier this year are present, a person can have a two to three fold increased risk of bowel cancer.

In a previous investigation, the researchers located a genetic region responsible for Hereditary Mixed Polyposis Syndrome (HMPS) - a condition that increases bowel cancer risk in Ashkenazi Jews. In this study, the search was narrowed down to try to find the specific genes responsible for HMPS by analysing the genomes of nearly 15,000 people, including nearly 8,000 bowel cancer cases.

The scientists didn't find any genes directly responsible for HMPS but instead found that the HMPS region contained other genes that increase bowel cancer risk in the general UK population.

The study was jointly led by Professor Ian Tomlinson from the London Research Institute and Professor Richard Houlston from The Institute of Cancer Research.

Professor Ian Tomlinson, joint lead researcher based at Cancer Research UK's London Research Institute said: "We're delighted to have taken our research forward to pin down genes that influence a person's risk of developing bowel cancer. Increasing our understanding of genes like this may make it possible for scientists to eventually develop ways of stopping many people at increased risk of bowel cancer from developing the disease altogether.

"Finding out that a region we thought was only relevant to bowel cancer risk in Ashkenazi Jews was also related to risk in the wider UK population is very important. This could help us understand how different variants of the same gene affect risk and how genes interact to increase overall risk."

Professor Richard Houlston, joint lead researcher based at The Institute of Cancer Research, said: "This is an exciting development in our understanding of how bowel cancer develops, a disease which kills more than 16,000 people in the UK each year. By pinpointing more genes which increase an individual's risk of bowel cancer we ultimately hope to improve diagnosis and treatment of this cancer."

The increased risk incurred as a result of these individual genetic faults is relatively small so genetic testing for these alone would not be worthwhile. But it may be possible to design a test for a combination of genes as more 'low risk' variants are found. Identifying people who have an increased risk of developing bowel cancer will improve prevention, diagnosis and treatment of the disease in the future.

Dr Lesley Walker, Cancer Research UK's director of cancer information, said: "Cancer Research UK is launching a series of genome wide studies, including searches for genes that influence lung and ovarian cancer risk. Discoveries like this will improve our understanding of cancer and help us to develop targeted screening and treatment for people at increased risk of the disease."