familial polyposis

家族性大腸腺腫症

WordNet

1. relating to or having the characteristics of a family; "children of the same familial background"; "familial aggregation"
2. occurring among members of a family usually by heredity; "an inherited disease"; "familial traits"; "genetically transmitted features" (同)genetic, hereditary, inherited, transmitted, transmissible

PrepTutorEJDIC

1. 家族の,家族特有の / 違伝的な,血統にあらわれる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/06 17:38:19」(JST)

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Familial adenomatous polyposis
Classification and external resources
Endoscopic image of sigmoid colon of patient with familial adenomatous polyposis.
ICD-10	C18, D12
ICD-9	211.3
ICD-O:	8220/0
OMIM	175100
DiseasesDB	4678
eMedicine	med/769
MeSH	D011125

CHRPE

Familial adenomatous polyposis (FAP) is 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 when left untreated.

Signs and symptoms

From early adolescence and onwards, patients with this condition develop hundreds to thousands of polyps. 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.

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).

Diagnosis

Micrograph of a tubular adenoma, the colorectal cancer precursor most commonly associated with FAP.

Making the diagnosis of FAP before the development of colon cancer is important not just for the individual, but also for the sake of other family members who may be affected. Colonoscopy is considered the diagnostic test of choice as it can provide not only a quantification of polyps throughout the colon but also a histologic diagnosis. Barium enema and virtual colonoscopy can suggest the diagnosis of FAP.

Once the diagnosis of FAP is made, close colonoscopic surveillance with polypectomy is required. Prophylactic colectomy is indicated if more than a hundred polyps are present, if there are severely dysplastic polyps, or if multiple polyps larger than 1 cm are present. When a partial colectomy is performed, colonoscopic surveillance of the remaining colon is necessary as the individual still carries significant risk of developing colon cancer.

Ultrasound of the abdomen and blood tests evaluating liver function are often performed to rule out metastasis to the liver.

Genetic testing provides the ultimate diagnosis in 95% of cases; genetic counseling is usually needed in families where FAP has been diagnosed. Testing may also aid in the diagnosis of borderline cases in families that are otherwise known to p34.3 and p32.1 (1p34.3-p32.1).

APC is a tumour suppressor gene, acting as a "gatekeeper" to prevent development of tumours. Mutation of APC also occurs commonly in incident cases of colorectal carcinoma, emphasizing its importance in this form of cancer.

Although the polyps are inherently benign, the first step of the two-hit hypothesis has already taken place: the inherited APC mutation. Often, the remaining "normal" allele is mutated or deleted, accelerating generation of polyps. Further mutations (e.g. in p53 or kRAS) to APC-mutated cells are much more likely to lead to cancer than they would in non-mutated epithelial cells.

The normal function of the APC gene product is still being investigated; it is present both the cell nucleus and the membrane. The canonical tumor-suppressor function of Apc is suppression of the oncogenic protein beta-catenin. However, other tumor-suppressor functions of Apc may be related to cell adherence and cytoskeleton organization.

MUTYH encodes DNA repair enzyme MYH glycosylase. During normal cellular activities, guanine sometimes becomes altered by oxygen, which causes it to pair with adenine instead of cytosine. MYH glycosylase fixes these mistakes by base excision repair, such that mutations do not accumulate in the DNA and lead to tumor formation. When MYH glycosylase does not function correctly, DNA errors may accrue to initiate tumorigenesis with a clinical presentation similar to that in patients with Apc mutations.

Genetics

Familial adenomatous polyposis can have different inheritance patterns and different genetic causes. When this condition results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. The incidence of malignancy in these cases approaches 100%. In most cases, an affected person has one parent with the condition.

Mutations in the MUTYH gene are inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

Prenatal testing is possible if a disease-causing mutation is identified in an affected family member; however, prenatal testing for typically adult-onset disorders is uncommon and requires careful genetic counseling.

Because of the genetic nature of FAP, polyposis registries have been developed around the world. The purpose of these registries is to increase knowledge about the transmissibility of FAP, but also to document, track, and notify family members of affected individuals. One study has shown that the use of a registry to notify family members (call-ups) significantly reduced mortality when compared with probands. The St. Mark's polyposis registry is the oldest in the world, started in 1924, and many other polyposis registries now exist.

Animal models

The "Apc^Min" mouse model was described in 1990 and carries an Apc allele with a stop codon at position 850. Heterozygosity for this mutation results in a fully penetrant phenotype on most genetic backgrounds, with mice on a sensitive background developing over 100 tumors in the intestinal tract. The number and location of the intestinal tumors is modified by unlinked genes. Many other models have since appeared, including a model of attenuated FAP (the 1638N model) and several conditional mutants that allow for tissue-specific or temporal ablation of gene function. For more information see mouse models of colorectal and intestinal cancer.

In 2007, the "ApcPirc" rat model was isolated with a stop codon at position 1137. In contrast to the mouse models where >90% of tumors form in the small intestine, the Pirc rat forms tumors preferentially (>60%) in the large intestine, similar to the human clinical presentation.

Epidemiology

The incidence of the mutation is between 1 in 10,000 and 1 in 15,000 births. By age 35 years, 95% of individuals with FAP (>100 adenomas) have polyps. Without colectomy, colon cancer is virtually inevitable. The mean age of colon cancer in untreated individuals is 39 years (range 34–43 years).

Treatment

Colectomy specimen showing numerous polyps throughout the large bowel.

Treatment for FAP depends on the genotype. Most individuals with the APC mutation will develop colon cancer by the age of 40. Therefore, prophylactic surgery is generally recommended before the age of 25. There are several surgical options that involve the removal of either the colon or both the colon and rectum. The decision to remove the rectum depends on the number of polyps in the rectum as well as the family history. If the rectum has few polyps, the colon is removed and the small bowel (ileum) is connected to the rectum (ileorectal anastomosis). If the rectum is involved then the colon and rectum are removed and a patient may require an ileostomy (permanent stoma where stool goes into a bag on the abdomen) or have an ileo-anal pouch reconstruction.

Various medications are being investigated for slowing malignant degeneration of polyps, most prominently the non-steroidal anti-inflammatory drugs (NSAIDs). The NSAIDS have been shown to significantly decrease the number of polyps but do not usually alter management since there are still too many polyps to be followed and treated endoscopically.

References

External links

• GeneReviews/NCBI/NIH/UW entry on APC-Associated Polyposis Conditions
• Cancerindex entry on the APC gene
• Familial adenomatous polyposis - NIH Genetics Home Reference
• Cancer.Net: Familial Adenomatous Polyposis
• Cancer.Net: Attenuated Familial Adenomatous Polyposis
• Familial Adenomatous Polyposis - eMedicine Gastroenterology
• Colon, Polyposis Syndromes
• www.fapgene.org.uk
• National Cancer Institute: Genetics of Colorectal Cancer information summary
• http://www.polyposisregistry.org.uk/

UpToDate Contents

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• 1. 家族性腺腫性ポリポーシスの臨床症状および診断 clinical manifestations and diagnosis of familial adenomatous polyposis
• 2. 家族性腺腫性ポリポーシスおよびMUTYH 関連ポリポーシス：患者および家族の
  スクリーニングおよびマネージメント familial adenomatous polyposis and mutyh associated polyposis screening and management of patients and families
• 3. ポイツ・イェガース症候群および若年性ポリポーシス：患者および家族のスクリーニング
  およびマネージメント peutz jeghers syndrome and juvenile polyposis screening and management of patients and families
• 4. 大腸癌のスクリーニング：家族歴によるリスク上昇の可能性がある患者における戦略 screening for colorectal cancer strategies in patients with possible increased risk due to family history
• 5. 大腸癌切除術の外科腫瘍学の原則 surgical oncologic principles for the resection of colon cancer

English Journal

• Familial adenomatous polyposis with concurrent metastatic appendiceal carcinoid and ovarian cystoadenoma.

• Kulkarni KP, Desai S, Chiu B, Sergi C.SourceDepartment of Pediatric Oncology, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada.
• Pediatric blood & cancer.Pediatr Blood Cancer.2011 Oct;57(4):702-3. doi: 10.1002/pbc.23150. Epub 2011 Jun 16.
• PMID 21681927

• Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea.

• Kim KM, Lee EJ, Ha S, Kang SY, Jang KT, Park CK, Kim JY, Kim YH, Chang DK, Odze RD.SourceDepartments of *Pathology †Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ‡Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
• The American journal of surgical pathology.Am J Surg Pathol.2011 Sep;35(9):1274-86.
• Abundant recent data suggest that sessile serrated adenoma/polyp (SSA/P) is an early precursor lesion in the serrated pathway of carcinogenesis. It is believed that SSA/Ps develop cancer by an SSA/P-dysplasia-carcinoma sequence. Hyperplastic polyps (HPs) share some histologic and molecular character
• PMID 21836485

Japanese Journal

• 大腸癌の危険因子 遺伝性大腸癌--家族性大腸腺腫症,MUTYH関連ポリポーシス,およびリンチ症候群 (大腸癌--最新の研究動向) -- (大腸癌の疫学)

• 岩間 毅夫,石田 秀行
• 日本臨床 69(-) (997), 59-64, 2011-04
• NAID 40018805495

• 症例 結腸全摘術,回腸直腸吻合術後の残存直腸病変に対し腹会陰式直腸切断術を施行した家族性大腸腺腫症の4例

• 池田 拓人,佛坂 正幸,日高 秀樹 [他]
• 外科 73(2), 219-221, 2011-02
• NAID 40018276414

Related Links

• Familial adenomatous polyposis - Wikipedia, the free encyclopedia

Familial adenomatous polyposis (FAP) is 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 when ...

Related Pictures

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★リンクテーブル★

リンク元	「家族性大腸腺腫症」
関連記事	「familial」「polyposis」

「家族性大腸腺腫症」

　　[★]

英

familial adenomatous polyposis, FAP

同

家族性大腸ポリポーシス ,familial polyposis coli, FPC, 家族性大腸ポリープ症, familial adenomatous polyposis coli

家族性ポリポーシス familial polyposis syndrome familial polyposis

関

大腸ポリポーシス

• familial polyposis syndrome

• familial adenomatous polyposis：APC gene
• Peutz-Jeghers syndrome：LKB1 gene
• Cowden syndrome：PTEN gene

概念

• 癌抑制遺伝子APC geneのloss of functionにより、大腸全体にびまん性に腺腫を生ずる。

分類

• 家族性大腸腺腫症のうち、以下の合併症を伴う物はそれぞれ家族性大腸腺腫症の下位概念として名称が与えられている

• ガードナー症候群 Gardner syndrome：多発性骨腫、軟部組織腫瘍 (YN.A.-74)
• ターコット症候群 Turcot syndrome ：中枢神経系腫瘍 (YN.A.-74)

SSUR.546によると、Garder症候群 ≒ 家族性大腸腺腫症。すなわち「古典的なGardner症候群の類似疾患である」(SSUR.546)

疫学

• 70%が遺伝性で、30%が孤発性。

遺伝形式

• 常染色体性優性遺伝

症状

合併症

• 消化管：大腸。60-70%の症例で　→　小腸・胃(胃底腺領域)・十二指腸
• 消化管外：顎骨内骨腫、顎骨以外の骨病変、網膜色素斑、体表の軟部組織腫瘍、デスモイド腫瘍、歯牙腫、甲状腺癌、子宮癌

予後

• 大腸癌は20歳ごろから発生、40歳で50%リスク、60歳でほぼ全例。癌により死亡する平均の年齢は42歳。(YN.A-74)

「familial」

　　[★]

• adj.

• 家族性の、家系性の、家族の

関

family、family member、household、kindred

　 　 　

「polyposis」

　　[★] ポリープ症、ポリポーシス