Polyposis, familial adenomatous

Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC)... 

Adenomatous polyposis coli (APC) gene A tumor suppressor gene, acting as a gatekeeper to prevent development of tumors. A familial cancer syndrome called FAP, or familial adenomatous polyposis, is caused by mutations in APC. Mutation of APC also occurs commonly in sporadic cases of colorectal carcinoma. 

Familial adenomatous polyposis An inherited condition in which numerous polyps form, mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs 100% of the time when not treated. 

Primary prevention is aimed at preventing colorectal cancer in an at-risk population. To date, the only strategy shown to reduce the risk is chemoprevention with celecoxib in people with familial adenomatous polyposis. 

Secondary prevention is aimed at preventing malignancy in a population that has already manifested an initial disease process. Secondary prevention includes procedures ranging from colonoscopic removal of precan-cerous polyps detected during screening colonoscopy to total colectomy for high-risk individuals (e.g., familial adenomatous polyposis). 

Tonelli F, Ficari F, Valanzano R, Brandi ML (2003) Treatment of desmoids and mesenteric fibromatosis in familial adenomatous polyposis with raloxifene. Tumore 89 391-396... 

Without regard to therapy, potentially valuable diagnostic tests are available for presymptomatic evaluation of risk of breast cancer due to predisposition from BRCA 1 or BRCA 2 and of colon cancer related to familial adenomatous polyposis (APC gene) or hereditary nonpolyposis mismatch repair genes (MSH 2). Genetic predisposition to Alzheimer disease associated with ApoE4 is neither sufficient nor necessary to lead to the clinical condition, and no definitive therapy is available. 

Persons with familial adenomatous polyposis are at 105,106 increased risk for adenomas and cancers of the small and large intestines. In the small intestine, these lesions occur mainly around the Ampulla of Vater, where their distribution parallels mucosal exposure to bile. 

D. G. Jagelman, J. J. DeCosse and H. J. Bussey, Upper gastro-intestinal cancer in familial adenomatous polyposis, Lancet, 1988, 1(8595), 1149. 

A. D. Spigelman, C. B. Williams, I. C. Talbot, P. Domizio and R. K. Phillips, Upper gastro-intestinal cancer in patients with familial adenomatous polyposis, Lancet, 1989, 2(8666), 783. 

N. N. Mahmoud, A. J. Dannenberg, R. T. Bilinski, J. R. Mestre, A. Chadburn, M. Churchill, C. Martucci and M. M. Bertagnolli, Administration of an unconjugated bile acid increases duodenal tumours in a murine model of familial adenomatous polyposis, Carcinogenesis, 1999, 20(2), 299. 

Steinbach G, Lynch P, Phillips R, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000 29 1946-1952. 

Epidemiological evidence reveals that individuals who take aspirin or NSAIDs have a 40-50% reduced risk of developing colon cancer and its nonmalignant precursor, the adenomatous polyp (4,43-46). Familial adenomatous polyposis (FAP) is a disease inher-... 

Familial adenomatous polyposis— An inherited disease of the colon in which many small growths develop in the colon and can turn into cancer. Genetic tests are available for this disease. 

Mechanism of Action An NSAID that inhibits cyclooxygenase-2, the enzyme responsible for prostaglandin synthesis. Mechanism of action in treating familial adenomatous polyposis is unknown. Therapeutic Effect Reduces inflammation and relieves pain. 

Familial adenomatous polyposis PO 400 mg twice daily (with food). 

Celecoxib leads to a significant reduction in the number of colorectal polyps in patients with familial adenomatous polyposis in a 6-months study (Steinbach etal., 2000). 

Familial adenomatous polyposis 574 Faraday, numerical value of 283 Farnesyl group 402, 559 Fat(s). See also Triacylglycerol (triglyceride) composition of 380 hydrolysis of 507 Fatty acid(s) 380-382 activation of 512 acyl CoA, derivatives of 507 biosynthesis of 722 branched chain 381 cyclopropane-containing 399 essential 721 in lipids 380 names of, table 380 oxidation 511 pKa values of 380 stability of 589... 

Chapters 11 and 31. Since cancers contain multiple mutations, they are complex diseases. However, many specific susceptibility loci are being located, including some for breast cancer (Box 11-D),392 prostate cancer,393 and familial adenomatous polyposis, a hereditary disease leading to colon cancer.388 394 Cancer has long been known to be associated with chromosome instability including deletion and insertion mutations at simple repeat sequences, frame-shift mutations,395 DNA breakage, translocation,396 and losses or gains of whole chromosomes 397... 

There are two major forms of hereditary susceptibility to colon cancer.00 Familial adenomatous polyposis is caused by defects in the APC gene (see Chapter 32). The more common hereditary nonpolyposis colorectal cancer (HNPCC), which includes many endometrial, stomach, and urinary tract tumors, results from defects in DNA mismatch repair. -)) The proteins hMSH2 and hMSLl are homologs of the E.coli MutS and MutL (main text). 

A Japanese girl aged 20 years, who had been legitimately treated with oxymetholone (30 mg/day) for 6 years for aplastic anemia, developed a hepatic adenoma (53). In this case, in contrast to some earlier reports, there was a predisposing factor in the form of familial adenomatous polyposis. 

Note FAP familial adenomatous polyposis ACF aberrant crypt foci FAD focal areas of dysplasia B[a]P benzo[a]pyrene DMBA 7,I2-dimethylbenz[a]nthracene TPA 12-O-tetradecanoyl-phorbol-13-acetate NNK 4-(methyl-nitrosamino)-I-(3-pyridyl)-l-butanone NQO 4-mtroquinoline 1-oxidase DMAB 3,2 -dimethyl-4-aminobiphenol PhIP 2-amino-l-methylimidazo[4,5-b]pyridine DHPN 2,2 -dihydroxy-di-n-propylnitrosamine EHEN jV-ethyl-jV-hydroxyethylnitrosamine. 

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