Rare form of hereditary colon cancer identified

Scientists have identified a new rare form of hereditary colon cancer that is caused by a genetic mutation that was previously unknown.
The formation of large numbers of polyps in the colon has a high probability of developing into colon cancer. The appearance of polyps is often due to a hereditary cause and the disease can occur in multiple family members.
Researchers from University Hospital Bonn in Germany discovered genetic changes in the MSH3 gene in patients and identified the rare form of hereditary colon cancer.
Colon polyps form like mushroom-shaped growths from the mucosa and are several millimetres to centimetres in size.

They are benign and generally do not cause any symptoms - however, they can turn into malignant tumours (colon cancer).
Physicians refer to the development of a large number of polyps in the colon as "polyposis." Scientists have already discovered several genes associated with a polyposis.

"However, about one-third of families affected by the disease do not have any abnormalities in these genes," said Stefan Aretz, from the University of Bonn Hospital.
Researchers, including those from the Yale University in the US, and the Frankfurt University Hospital, studied the genetic material (DNA) of more than 100 polyposis patients using blood samples.

In each patient, all of the about 20,000 protein-coding genes known were examined. Scientists found the rare, possibly relevant genetic changes out of the gigantic quantity of data.
In two patients, genetic changes (mutations) were discovered in the MSH3 gene on chromosome 5.
"The challenge is proving the causal connection between the mutations in this gene and the disease," said Aretz.
Siblings with the disease have to have these same MSH3 mutations as the patient who was first examined, but not the healthy relatives. Researchers found that to be the case.
They investigated the consequences for patients resulting from the loss of function of the MSH3 gene.

"It involves a gene for the repair of the genetic material. The mutations cause the MSH3 protein to not be formed," said Ronja Adam, from University Hospital Bonn.
Since the protein is missing in the cell nucleus of the patient's tissues, there is an accumulation of genetic defects. The mutations which are not repaired then predispose to the more frequent occurrence of polyps in the colon.
The newly discovered type of polyposis is not inherited dominantly, but instead recessively.
"This means that siblings have a 25 per cent chance of developing the disease; however, the parents and children of affected persons only have a very low risk of developing the disease," said Isabel Spier from the University Hospital Bonn.

Annual colonoscopy is the most effective cancer screening method for polyposis patients. As a result, the development of colon cancer can be effectively prevented.
By investigating the MSH3 gene, a clear diagnosis can be made in some other, previously unexplained polyposis cases.
The results were published in The American Journal of Human Genetics.