Doctors from the Imperial Cancer Research Fund, London, England have taken a step closer to identifying people who should be screened for bowel cancer. In new findings published this month (September 1998) in the Proceedings of the National Academy of Sciences* the research team confirm that two variants of the APC gene (a gene already associated with familial bowel cancer) do make people more susceptible to developing pre-cancerous polyps and thus predisposes them to bowel cancer.
Sir Walter Bodmer, head of the charity's Cancer and Immunogenetics Laboratory, Oxford explained: "We have found a new category of susceptibility to bowel cancer. What is interesting about these variants is that although they are hereditary their effect is not so strong as the other mutations which have already been identified with familial bowel cancer."
Dr Ian Frayling, Clincial Research Fellow with Imperial Cancer's Bowel Cancer Unit at St Mark's Hospital, added: "Not everyone who carries these variants of the APC gene will develop bowel cancer and so someone who carries the gene won't necessarily have a family history of the disease, but they might be at an increased risk of bowel cancer nonetheless."
Inherited mutations in the APC gene are responsible for a condition called Familial Adenomatous Polyposis (FAP) in which gene carriers get hundreds, often thousands, of polyps in their bowel and if the condition is not treated by surgery bowel cancer will develop. FAP is very rare (1 in 8000 individuals), but accounts for about one half a per cent of bowel cancer.
Added Dr Ian Tomlinson, head of Imperial Cancer's Molecular and Population Genetics Laboratory: "These new variants have a much more subtle effect and could be more common than the ones responsible for FAP. Someone who carries a standard APC gene mutation will have a risk of bowel cancer 40 times higher than normal. The risk for someone with one of these weaker variants may only be 5 times normal."
The next step will be to carry out larger studies to find out why only some of the carriers of these variants develop cancer. The doctors believe that environmental elements such as diet are probably involved, together with other genes. They also want to find out the exact risk these genes confer and the best way of identifying carriers.
Said Dr Frayling: "This is a definite lead on common genes that lead to bowel cancer. There is other evidence that there are other similar genes which carry this type of risk. Our findings bring us closer to the day when we will be able to identify those people who will gain the most from bowel screening and this could potentially save hundreds of lives from this disease."
Added Sir Walter Bodmer: "The only way to find other genes like these is to do what we did and look for mutations in genes which have a strong effect. This is an important finding because it is a general phenomenon and applies to other diseases, such as heart disease, which have genes that have a severe effect."
It is likely to be a number of years before a clinical test for these gene variants is available.
*The APC variants 11307K and E1317Q are associated with colorectal tumours, but not always with a family history. PNAS. 1 September 1998.
NOTES TO EDITORS
- Bowel cancer is the third most common cancer (excluding skin cancer) and the second most common cause of cancer death in the UK. It is the commonest non-smoking related cancer affecting both sexes. There are 31,300 new cases and 17,900 deaths in the UK every year.
- Bowel cancer is curable, especially when detected at an early stage. It is also preventable by the removal of pre-cancerous polyps.
- The research was carried out by researchers from the Imperial Cancer Research Fund's Colorectal Cancer Unit, Cancer and Immunogenetics Laboratory, and Molecular and Population Genetics Laboratory. Also on the team were doctors from the Kennedy-Galton Centre for Medical Genetics and the Wolfson Unit for Endoscopy at St Mark's Hospital, and the Dept of Clinical Genetics at Guy's Hospital.
- Sir Walter Bodmer is at the British Association's Annual Festival of Science, at Cardiff University, until Wednesday (9 September) afternoon. The BA Conference press office telephone number is: +44-1222-224490.
The Imperial Cancer Research Fund is dedicated to the understanding, prevention, treatment and cure of all forms of cancer. Its scientists and doctors are at the forefront of the worldwide effort to defeat the disease. The charity relies almost totally on voluntary funding to carry out its vital work.
Journal
Proceedings of the National Academy of Sciences