| Entity | Familial Adenomatous Polyposis (FAP) |
| Disease | Autosomal dominant disease in which patients develop thousands of colonic polyps during childhood and adolescence. Many of these will progress to cancers if not removed.
FAP encompasses other disease syndromes with extra-colonic manifestations. In Gardner Syndrome, patients may develop the following extra-intestinal manifestations: Gastric and duodenal malignancies. Cancer of the pancreas, biliary tree, and gallbladder. Hepatoblastoma. Congenital hypertrophy of the retinal pigment epithelium (CHRPE), a benign hyperpigmentation beneath the retina that is typically asymptomatic. Desmoid tumors, a tumor of the connective tissue that can cause morbidity and mortality by impinging on adjacent structures. Osteomas and dental abnormalities. Epidermoid cysts and other skin abnormalities. In a subset of patients with Turcot's syndrome, intestinal polyposis due to APC mutation is associated with brain tumors, especially meduloblastoma. |
| Prognosis | Without treatment, the life expectancy is in the early 40s due to colon cancer. Treatment consists of regular screening, with polypectomy of large lesions. Due to the large number of polyps, eventual complete colectomy with or without proctosigmoidectomy is needed. Regular use of the cyclooxygenase inhibitor Sulindac and possibly other member of this class of drugs reduces the number of polyps. About ten percent of patients also experience significant morbidity from desmoid tumors. |
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| Entity | Sporadic colorectal cancer |
| Disease | Somatic mutation of the APC gene is found in the majority of colorectal adenocarcinomas. Sporadic colorectal cancer is the third most frequent cancer in the world. |
| Prognosis | The prognosis depends on the stage of the disease. Stage I lesions are usually cured by surgery. There is controversy about the use of chemotherapy in Stage II disease. In Stage III disease, chemotherapy improves the five year survival from ~50% to ~60%. |
| Oncogenesis | Loss of normal APC function is known to be an early event in both familial and sporadic colon cancer pathogenesis, occurring at the pre-adenoma stage. Current discussion is focused on whether loss of APC function precedes, follows, or is entwined with chromosomal instability. Later events include abnormalities of K-ras and p53. Generally colon cancers show either chromosomal instability (CIN), which correlates with loss of APC function, or microsatellite instability (MIN), which correlates with loss of mismatch repair function, but not both. |
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