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Familial adenomatous polyposis (FAP) is an inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when left untreated. Three variants are known to exist, FAP and attenuated FAP (originally called “hereditary flat adenoma syndrome〔(Sovaria et al, June 1998: Genotype-Phenotype Correlations in Attenuated Adenomatous Polyposis Coli )〕) are caused by APC gene defects and autosomal recessive FAP (or MYH-associated polyposis) is caused by ''MUTYH'' gene defects. Of the three, FAP itself is the most severe and most common; although for all three, the resulting colonic polyps and cancers are confined to the colon wall and removal can greatly reduce the spread of cancer. The root cause of FAP is understood to be a genetic mutation—a flaw in the body's tumour suppressor genes that prevent development of tumours. The flaw allows numerous cells of the intestinal wall to develop into potentially cancerous polyps when they would usually reach the end of their life; inevitably one or more will eventually progress and give rise to cancer (7% risk by age 21, rising to 87% by age 45 and 93% by age 50). The flawed genes do not trigger cancer, but rather, they reduce the body's ability to protect against the risk of aged cells becoming cancerous. Even with the flawed gene, it may still take time before a cell actually does develop that is cancerous as a result, and the gene may in some cases still partially operate to control tumours, therefore cancer from FAP takes many years to develop and is almost always an adult-onset disease. The second form of FAP, known as attenuated familial adenomatous polyposis has the APC gene functional but slightly impaired. It is therefore somewhat able to operate as usual. Attenuated FAP still presents a high 70% lifetime risk of cancer (as estimated), but typically presents with far fewer polyps (typically 30) rather than the hundreds or thousands usually found in FAP,〔http://www.ncbi.nlm.nih.gov/books/NBK1345/〕 and arises at an age when FAP is usually no longer considered likely—typically between 40 and 70 years old (average 55〔http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis〕) rather than the more usual 30's upward. Because it has far fewer polyps, options for management may be different.〔 The third variant, autosomal recessive familial adenomatous polyposis or MYH-associated polyposis, is also milder and, as its name suggests, requires both parents to be 'carriers' to manifest the condition. In some cases FAP can manifest higher in the colon than usual (for example, the ascending colon, or proximal to the splenic flexure, or in the gastric or duodenal tracts〔) where they show no symptoms until cancer is present and greatly advanced. APC mutations have been linked to certain other cancers such as thyroid cancer. As the mutation causing FAP is genetic, it can be inherited hereditarily from either parent, and passed to children. A genetic blood test of the APC gene exists that can determine whether it is deficient, and therefore can predict the possibility of FAP. Individuals at risk (due to family links or genetic testing) are usually offered routine monitoring of the intestinal tract every 1 – 5 years for life, from early adulthood, to detect the slow-forming polyps and act if found, before they can pose a threat. International polyposis registries exists that track known cases of FAP or APC gene defects, for research and clinical purposes. Mutation of APC also occurs commonly in incident cases of colorectal carcinoma, emphasizing its importance in this form of cancer. ==Signs and symptoms== From early adolescence, patients with this condition gradually (and much of the time 'silently') develop hundreds to thousands of colorectal polyps (and sometimes polyps elsewhere)—small abnormalities at the surface of the intestinal tract, especially in the large intestine including the colon or rectum. These may bleed, leading to blood in the stool. If the blood is not visible, it is still possible for the patient to develop anemia due to gradually developing iron deficiency. If malignancy develops, this may present with weight loss, altered bowel habit, or even metastasis to the liver or elsewhere. FAP can also develop 'silently' in some individuals, giving few or no signs until it has developed into advanced colorectal cancer. Because familial polyposis develops very gradually over years, and can also manifest in an 'attenuated' form even slower, polyps resulting from FAP can lead to cancer developing at any point from adolescence to old age. Depending on the nature of the defect in the APC gene, and whether it is the full or attenuated form, familial polyposis may manifest as polyps in the bowel, or in the colon, or in the duodenal tract, or in any combination of these. Therefore an absence of polyps in, for example, the rectum, may not of itself be sufficient to confirm absence of polyps. It may be necessary to consider and visually examine other possible parts of the intestinal tract. Colonoscopy is preferred over sigmoidoscopy for this, as it provides better observation of the common right-side location of polyps.〔 The genetic determinant in familial polyposis may also predispose carriers to other malignancies, e.g., of the duodenum and stomach (particularly ampullary adenocarcinoma). Other signs that may point to FAP are pigmented lesions of the retina ("CHRPE—congenital hypertrophy of the retinal pigment epithelium"), jaw cysts, sebaceous cysts, and osteomata (benign bone tumors). The combination of polyposis, osteomas, fibromas and sebaceous cysts is termed ''Gardner's syndrome'' (with or without abnormal scarring).〔 〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「familial adenomatous polyposis」の詳細全文を読む スポンサード リンク
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