Genetic Syndromes

PDF Download 186KB

Six percent of colorectal cancers are due to inherited genetic syndromes. These genetic syndromes typically increase the risk of developing polyps. The most common of these genetic syndromes is Lynch Syndrome (also called Hereditary Non-Polypsosis Colorectal Cancer). Patients with Lynch syndrome are particularly at risk adenomatous polyps as well as sessile serrated adenomas (SSI), both of which can progress to cancer.

Other genetic syndromes associated with a large number of polyps (polyposis) and hence risk of colorectal cancer include an autosomal dominant condition Familial Adenomatous Polyposis (FAP) where there are over a 100 polyps in the colon (figure 1), and a weaker version of it called attenuated Familial Adenomatous Polyposis (FAP), where there are less than a 100 polyps, and an autosomal dominant condition called MYH-associated polyposis (MAP).

Less common are the hamartomatous polyposis syndromes which include Peutz Jegher’s syndrome, Juvenile polyposis, and Cowden disease, which have a slightly increased risk of colorectal cancer.

Figure 1. Polyposis of the colon with increased risk of cancer formation.

Individuals with a strong family history of colorectal cancer have an inherited genetic predisposition. The aim should therefore be to correctly assess their risk, provide genetic counselling, genetic testing, and cancer preventative strategies and surgical treatment based on the particular genetic syndrome.

Risk assessment is based on thorough history taking, identifying cancer-affected member of the family pedigree. The germ-line mutation may ultimately be made by testing an appropriate family member.

Cancer mortality is clearly reduced in individuals with an inherited cancer syndrome who actively participate in regular screening and surveillance programs such as regular colonoscopies and gastroscopies.

Inherited genetic syndromes not only have an increased risk of colorectal cancer, but also have an increased risk of cancer in other extra-colonic sites. For this reason management of these multi-system disorders does not fall within the boundaries of a single specialty, but requires involvement from surgeons as well as gastroenterologists, gynaecologists, oncologist, general practitioners, and molecular geneticists. Multidisciplinary familial cancer services are important in coordinating care in a multidisciplinary manner by providing the following support:
Ascertainment of families
Construction of family pedigrees
Verification of clinical and pathological data
Collection of tissue and blood samples
Maintenance of confidential and secure database of present and future generations of a family
Liaison with relevant health care professionals
Education and support and counselling
Identification of at-risk family members
Coordination of genetic counselling and testing
Coordination of cancer screening
Facilitation of multidisciplinary clinical management
Documentation of extended follow up

State-based familial cancer registers have been established in Australia.