There are several hereditary disorders that are associated with increased risk of developing colorectal cancer. This include familial adenomatous polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC) and several other less known genetic disorders.
Familial adenomatous polyposis
Most notable example of a genetic disorder with increased risk of development of colorectal cancer is familial adenomatous polyposis (FAP). This disorder is inherited as an autosomal dominant trait (which means sons and daughters of a person affected by this disease have 50 percent chance of inheriting this disorder). Patients who have this genetic abnormality typically develop multiple (thousands of) adenomatous polyps in the large intestine including the rectal area. In about half of these patients the adenomatous polyps will start appearing by the age of 50, and in almost 80 percent of the patients the polyps are visible by age 35. If no measures were taken almost all of these patients with multiple polyps will develop colorectal cancer by the age of 35 to 43. In order to prevent the occurrence of colorectal cancer in these patients who have already developed multiple polyposis, physicians would recommend a prophylactic total colectomy at the time of development of multiple polyposis. The inherited abnormality in these patients with familial adenomatous polyposis (FAP) is located at 5q21 and is called APC gene.
Hereditary non-polyposis colorectal cancer (HNPCC)
Patients who have inherited this genetic abnormality do not typically develop colonic polyps (hence the name non-polyposis). It is not possible to identify patients who have inherited this genetic mutation by physical traits or physical examination and the only way to identify this group of patients may be genetic testing. A strong family history may suggest a possibility of hereditary non-polyposis colorectal cancer (HNPCC) in a family and this would need confirmation by genetic testing. The Amsterdam criteria was developed in an attempt to identify families who may have this type of mutation, so that they can be streamlined and brought for genetic testing. The following are the Amsterdam criteria.
Families, which meet all the three criteria, are considered to be high risk of having an HNPCC mutation and are strongly recommended to have genetic test done. The abnormality for hereditary non-polyposis colorectal cancer (HNPCC) is located in MSH2 or MLH1 gene.
- Three or more relatives with a histologically verified HNPCC associated cancer (colorectal, endometrial, small bowel, ureter, or renal pelvis) one of them is the first degree relative of the other two.
- Colorectal cancer involving at least two generations
- One or more colorectal cancers diagnosed before the age of 50