Colon Cancer and Polyposis FAP – HNPPC ?
Certain groups of patients have a predisposition to the development of cancer of the large bowel. These identifiable high-risk cohorts also have a greater possibility for early intervention and cancer prevention and include patients with inherited conditions such as familial adenomatous polyposis (FAP), hereditary nonpolyposis colon cancer (HNPCC), and ulcerative colitis. Patients with FAP (frequency estimated at 1:7,000 to 10,000 live births) have a lifetime risk of the development of colon cancer that approaches 100%. The disease is inherited as an autosomal dominant trait, and affected individuals will transmit this predisposition, with each of their offspring having nearly a 50% chance of developing polyposis coli. The gene that causes FAP (adenomatous polyposis coli [APC] gene) resides on chromosome 5 and has been cloned and sequenced.
Occasionally, patients with polyposis are found to have no affected family members. Presumably, this represents a new mutation.Numerous molecular, biologic, and biochemical screening tests have attempted to define better predictors of mucosal transformation in such patients.However, without a proven screening test, the offspring of affected patients should have annual or biannual colonoscopy or air-contrast barium enema studies starting at age 15 years. Screening should continue until about 30 years of age. The median age at which colon cancer is diagnosed in polyposis patients is approximately 40 years, which is approximately 2 decades earlier than its occurrence in the general population. Because stage-specific survival of colon cancer appears to be the same for polyposis patients as for those who have sporadic bowel cancer, total colectomy at the time polyposis is diagnosed remains the treatment of choice, particularly because recent technical modifications have allowed the surgeon to remove all of the large bowel mucosa without sacrificing continence.
Other polyposis variants have been recorded, including Turçot’s syndrome (polyposis and malignant central nervous system tumors) and Gardner’s syndrome, which feature not only multiple polyposis associated with osteomas of the jaw and other bones, cutaneous fibromas, and occasionally desmoids of the abdomen after surgery but also carcinoma of the ampulla of Vater and the thyroid gland. All of these syndromes, in which true polyps of the bowel proliferate, predispose to colon cancer.
Patients with hamartomatous polyps of the intestine, as in the dominantly inherited Peutz-Jeghers syndrome and juvenile polyposis coli, do not have a particularly high risk of colon or rectal adenocarcinoma. Aggressive screening and surgical management for these inherited polyposis diseases are not necessary.
HNPCC, a familial disorder characterized by a high incidence of colon cancer without the excessive polyps identified in FAP, may account for up to 6% of colon cancers.HNPCC encompasses two syndromes: Lynch I (colonic tumors only) and Lynch II (colonic and extra colonic [endometrial, ovarian, gastric, breast, and hepatobiliary] adenocarcinomas). Diagnostic criteria for identifying individuals with HNPCC have been established . The molecular genetic marker reflective of HNPCC is microsatellite instability, which is a consequence of mutations in DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2). Patients with HNPCC develop colon cancer at an early age with a propensity for right-sided lesions. In retrospective reviews, survival for this cohort is reportedly better than that for patients with sporadic colon cancer, but this may reflect inherent bias with this type of analysis