Genetic mutations could collectively raise bowel cancer risk

Nov 4 2004

Cancer Research UK scientists at the University of Oxford have found that a number of genetic mutations could collectively raise bowel cancer risk, reporting their findings in the journal PNAS.

About four per cent of bowel cancer cases are caused by mutations in individual genes, such as the APC gene. But scientists believe an additional 20 per cent of cases are caused by the combined effect of many genetic mutations, most of which are insignificant alone.

The team, led by renowned scientist Sir Walter Bodmer, hopes that development of a sophisticated blood test based on new knowledge about these mutations could enable doctors to identify and monitor people at high risk of the disease.

Most bowel cancers develop from polyps in the gut, so having multiple polyps puts individuals at higher risk of developing the disease.

The team compared blood samples from 124 patients who had multiple polyps in their gut with samples from 483 members of the general population.

They found a range of genetic variants in the group with multiple polyps, each twice as frequent on average as in the control group. Each of these variants appears to increase the likelihood that individuals will develop polyps.

Sir Walter Bodmer, who conducted the research for Cancer Research UK, says: "Patients who had the genetic variants we studied were twice as likely to have multiple polyps in their gut than those who did not.

"Further work will identify additional similar key variant genes that raise a person's risk of bowel cancer. I believe we could eventually exploit this knowledge to develop a blood test to identify those at high risk of the disease."

Doctors could actively monitor such patients for cancerous changes in their polyps, and remove them before they develop into bowel cancer.

Further research using samples from a larger number of patients is now planned to confirm associations between particular genetic mutations and multiple polyps. This work will also lead to the discovery of other mutations responsible for inherited susceptibility to bowel cancer.

Sir Walter adds: "Cancer susceptibility is most probably due to the cumulative effect of many individually infrequent genetic variants, rather than a modest effect of one or more common variants. This could help explain why it has been difficult to identify specific genes that confer genetic susceptibility to cancer, and also to conditions as varied as schizophrenia and Alzheimer's disease."

Dr Lesley Walker, Director of Cancer Information at Cancer Research UK, says: "Introduction of a national screening programme for bowel cancer was announced last week. People over 60 will from April 2006 be screened using a test known as the faecal occult blood test (FOBT) followed by colonoscopy to detect early cancers and polyps. However, scientists will continue investigating a range of screening techniques in order to save as many lives as possible.

"Finding the genetic mutations that cause around 20 per cent of bowel cancers will be an important advance in our understanding of the disease, and could also help in efforts to prevent the disease in those at high risk."

http://www.cancerresearchuk.org