CANCER RESEARCH UK funded scientists have found that people who carry rare mutations within both copies of a gene called MUTYH are 28 times more likely to develop bowel cancer compared to the general population, according to a study in the Journal of Clinical Oncology.
The scientists, at The Institute of Cancer Research(ICR), replicated previous findings that showed this increase in risk only exists if mutations are in both copies (called biallelic mutations) of the gene. The research also adds important insights into the controversy surrounding whether or not having just one mutation (or monoallelic mutation) does raise an individual's risk of bowel cancer.
In the largest study of its kind, they conclusively found that carriers of mutations in only one copy have no significant increase in risk for bowel cancer compared to that of the general population. They were able to demonstrate this by combining data from this study and other studies. In total they looked at the genetic makeup of more than 30,000 people.
The researchers looked for two mutations in the MUTYH gene, called Y179C and G396D, in over 9,000 bowel cancer patients and over 5,000 healthy individuals. The MUTYH gene codes for a DNA base excision repair protein which removes mistakes that build up in the DNA sequence.
They observed that all 27 people who carried biallelic mutations were in the bowel cancer group, and they accounted for 0.3 per cent of all bowel cancers in this study. They also found that these patients developed bowel cancer when they were relatively young - in their 50s. Most bowel cancers, over 80 per cent, occur in people aged 60 and over.
Although the contribution of biallelic mutations to the overall incidence of bowel cancer is not high, the risk of developing the disease is substantial.
Because of this young age and high risk for developing bowel cancer the researchers recommend that siblings of biallelic mutation carriers should have annual colonoscopy from as early as 20 years of age as they have a 25 per cent chance of also having the two genetic mutations.