This podcast discusses the inherited condition known as Familial Adenomatous Polyposis characterized by the development of abnormal growths called polpys in the lining of the large intestine. It describes how a mutation in a gene (in this case the APC gene) leads to the development of this adenomas (in other words polyps) and how the inheritance of this mutation can be observed in a family and adequate early screening can be done to increase chances of survival. This inherited condition has been linked to approximately 1 in100 cases of bowel cancer.

This podcast discusses the inherited condition known as Familial Adenomatous Polyposis characterized by the development of abnormal growths called polpys in the lining of the large intestine. It describes how a mutation in a gene (in this case the APC gene) leads to the development of this adenomas (in other words polyps) and how the inheritance of this mutation can be observed in a family and adequate early screening can be done to increase chances of survival. This inherited condition has been linked to approximately 1 in100 cases of bowel cancer.

Presenters: Drs Zaheer Moolla & Shakeel Kader

Surveillance gastroscopy in patient with FAP who has already had a pan-proctocolectomy.

Familial Adenomatous Polyposis (FAP) is an inherited genetic condition which predisposes individuals to the formation of colonic polyps. Individuals with the condition typically end up with a colon that is full of polyps.

Familial Adenomatous Polyposis is caused by an inherited mutation in one of the copies of the gene for the APC protein (Adenomatous Polyposis Coli protein, named such because of its involvement in this condition). This protein is involved in an important intracellular signalling mechanism called the Wnt/Beta-Catenin pathway which is involved in controlling cellular division. Mutations in the APC genes result in loss of function of the protein. If both genes are lost inside a cell, then that cell will have no functional APC protein. This results in complete disfunction of the Wnt/Beta-Catenin pathway and the cell ends up dividing excessively producing a whole population of cells with the same mutation. When this occurs in colonic epithelial cells, it physically manifests as a polyp.

An individual with two normal inherited APC genes needs a colonic epithelial cell to have suffered loss of function mutations of both APC genes in order for a polyp to arise. Individuals with Familial Adenomatous Polyposis have one inherited mutation already. So for their colonic epithelial cells it is only necessary for them to acquire one mutation in order for a polyp to arise. This one hit is far more likely than the two hits it would take for someone without the inherited mutation. Hence it occurs far more frequently and individuals with FAP end up with far more polyps.

In this video we discuss the Wnt / Beta-catenin pathway in detail and where the APC protein fits into this pathway. From this we can understand how loss of the APC protein would lead to excessive cell division. We then discuss FAP in which the inherited loss of one of the APC genes means that if a cell were to develop a mutation in the second of the two genes it would lose control of this pathway and excessive division would follow. Indeed this is what happens for these individuals and the most predisposed location for the second genetic hit to occur is the colonic epithelial cells and this is where they end up with multiple tumours.

Familial Adenomatous Polyposis (FAP) is an inherited genetic condition which predisposes individuals to the formation of colonic polyps. Individuals with the condition typically end up with a colon that is full of polyps.

Familial Adenomatous Polyposis is caused by an inherited mutation in one of the copies of the gene for the APC protein (Adenomatous Polyposis Coli protein, named such because of its involvement in this condition). This protein is involved in an important intracellular signalling mechanism called the Wnt/Beta-Catenin pathway which is involved in controlling cellular division. Mutations in the APC genes result in loss of function of the protein. If both genes are lost inside a cell, then that cell will have no functional APC protein. This results in complete disfunction of the Wnt/Beta-Catenin pathway and the cell ends up dividing excessively producing a whole population of cells with the same mutation. When this occurs in colonic epithelial cells, it physically manifests as a polyp.

An individual with two normal inherited APC genes needs a colonic epithelial cell to have suffered loss of function mutations of both APC genes in order for a polyp to arise. Individuals with Familial Adenomatous Polyposis have one inherited mutation already. So for their colonic epithelial cells it is only necessary for them to acquire one mutation in order for a polyp to arise. This one hit is far more likely than the two hits it would take for someone without the inherited mutation. Hence it occurs far more frequently and individuals with FAP end up with far more polyps.

In this video we discuss the Wnt / Beta-catenin pathway in detail and where the APC protein fits into this pathway. From this we can understand how loss of the APC protein would lead to excessive cell division. We then discuss FAP in which the inherited loss of one of the APC genes means that if a cell were to develop a mutation in the second of the two genes it would lose control of this pathway and excessive division would follow. Indeed this is what happens for these individuals and the most predisposed location for the second genetic hit to occur is the colonic epithelial cells and this is where they end up with multiple tumours.

The risks of developing CRC is approximately 70% in patients with familial adenomatous polyposis (FAP)