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the basic unit of money in Costa Rica; equal to 100 centimos (同)Costa Rican colon
the basic unit of money in El Salvador; equal to 100 centavos (同)El Salvadoran colon
a punctuation mark (:) used after a word introducing a series or an example or an explanation (or after the salutation of a business letter)
the part of the large intestine between the cecum and the rectum; it extracts moisture from food residues before they are excreted
type genus of the family Cancridae (同)genus Cancer
the fourth sign of the zodiac; the sun is in this sign from about June 21 to July 22 (同)Cancer the Crab, Crab
(astrology) a person who is born while the sun is in Cancer (同)Crab
a small zodiacal constellation in the northern hemisphere; between Leo and Gemini
any malignant growth or tumor caused by abnormal and uncontrolled cell division; it may spread to other parts of the body through the lymphatic system or the blood stream (同)malignant neoplastic disease
a pass between mountain peaks (同)gap

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コロン(:)(句読点の一種で,文中においてセミコロン以上を分離を示すほか,対照,例証,引用文などを示すのに用いる)
(大腸の)結腸[部]
〈U〉〈C〉『がん』 / 〈U〉〈C〉害悪 / 《Cancer》(星座の)カニ座
世襲の,親譲りの / 遺伝的な,遺伝性の
(山脈の)鞍部(あんぶ),山あい

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/05 22:57:00」(JST)

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Lynch syndrome (HNPCC or hereditary nonpolyposis colorectal cancer ) is an autosomal dominant genetic condition that has a high risk of colon cancer^[1] as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. It is a type of cancer syndrome.

Terminology

Henry T. Lynch, Professor of Medicine at Creighton University Medical Center, characterized the syndrome in 1966.^[2] In his earlier work, he described the disease entity as "cancer family syndrome." The term "Lynch syndrome" was coined in 1984 by other authors, and Lynch himself coined the term HNPCC in 1985. Since then, the two terms have been used interchangeably, until more recent advances in the understanding of the genetics of the disease led to the term HNPCC falling out of favour.^[3]

Other sources reserve the term "Lynch syndrome" when there is a known DNA mismatch repair defect, and use the term "Familial colorectal cancer type X" when the Amsterdam criteria are met but there is no known DNA mismatch repair defect.^[4] The putative "type X" families appear to have a lower overall incidence of cancer and lower risk for non-colorectal cancers than families with documented DNA mismatch repair deficiency.^[5] About 35% of patients meeting Amsterdam criteria do not have a DNA-mismatch-repair gene mutation.^[6]

Complicating matters is the presence of an alternative set of criteria, known as the "Bethesda Guidelines."^[7]^[8]^[9]

Classification

Three major groups of MSI-H (MSI, MicroSatellite Instability) cancers can be recognized by histopathological criteria:

right-sided poorly differentiated cancers
right-sided mucinous cancers
adenocarcinomas in any location showing any measurable level of intraepithelial lymphocyte (TIL)

In addition, HNPCC can be divided into Lynch syndrome I (familial colon cancer) and Lynch syndrome II (HNPCC associated with other cancers of the gastrointestinal tract or reproductive system).^[10]

Signs and symptoms

Tumoral predisposition

Colorectal cancer
Endometrial carcinoma
Digestive adenoma: Gastric adenoma, pyloric gland adenoma,^[11] duodenal adenoma, intestinal adenoma

Risk of colon cancer

Individuals with HNPCC have about an 80% lifetime risk for colon cancer. Two-thirds of these cancers occur in the proximal colon. The mean age of colorectal cancer diagnosis is 44 for members of families that meet the Amsterdam criteria. Also, women with HNPCC have an 80% lifetime risk of endometrial cancer. The average age of diagnosis of endometrial cancer is about 46 years. Among women with HNPCC who have both colon and endometrial cancer, about half present first with endometrial cancer, making endometrial cancer the most common sentinel cancer in Lynch syndrome.^[12] In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40 years. Other HNPCC-related cancers have been reported with specific features: the urinary tract cancers are transitional carcinoma of the ureter and renal pelvis; small bowel cancers occur most commonly in the duodenum and jejunum; the central nervous system tumor most often seen is glioblastoma.

Genetics

HNPCC is inherited in an autosomal dominant fashion.

The hallmark of HNPCC is defective DNA mismatch repair, which leads to microsatellite instability, also known as MSI-H (the H is "high"). MSI is identifiable in cancer specimens in the pathology laboratory.^[13] Most cases result in changes in the lengths of dinucleotide repeats of the nucleobases cytosine and adenine (sequence: CACACACACA...).^[14]

HNPCC is known to be associated with mutations in genes involved in the DNA mismatch repair pathway.

OMIM name	Genes implicated in HNPCC	Frequency of mutations in HNPCC families	Locus	First publication
HNPCC1 (120435)	MSH2	approximately 60%	2p22	Fishel 1993^[15]
HNPCC2 (609310)	MLH1	approximately 30%	3p21	Papadopoulos 1994^[16]
HNPCC5	MSH6	7-10%	2p16	Miyaki 1997^[17]
HNPCC4	PMS2	relatively infrequent,^[18] <5%^{[citation needed]}	7p22
HNPCC3	PMS1	case report^[19]	2q31-q33
HNPCC6	TGFBR2	case report^[20]	3p22
HNPCC7	MLH3	disputed^[21]	14q24.3

Patients with MSH6 mutations are more likely to be Amsterdam criteria II-negative.^[22] The presentation with MSH6 is slightly different than with MLH1 and MSH2, and the term "MSH6 syndrome" has been used to describe this condition.^[23] In one study, the Bethesda guidelines were more sensitive than the Amsterdam Criteria in detecting it.^[24]

Up to 39% of families with mutations in an HNPCC gene do not meet the Amsterdam criteria.^{[citation needed]} Therefore, families found to have a deleterious mutation in an HNPCC gene should be considered to have HNPCC regardless of the extent of the family history. This also means that the Amsterdam criteria fail to identify many patients at risk for Lynch syndrome. Improving the criteria for screening is an active area of research, as detailed in the Screening Strategies section of this article.

HNPCC is inherited in an autosomal dominant manner. Most people with HNPCC inherit the condition from a parent. However, due to incomplete penetrance, variable age of cancer diagnosis, cancer risk reduction, or early death, not all patients with an HNPCC gene mutation have a parent who had cancer. Some patients develop HNPCC de-novo in a new generation, without inheriting the gene. These patients are often only identified after developing an early-life colon cancer. Parents with HNPCC have a 50% chance of passing the genetic mutation on to each child.

Screening

Genetic testing for mutations in DNA mismatch repair genes is expensive and time-consuming, so researchers have proposed techniques for identifying cancer patients who are most likely to be HNPCC carriers as ideal candidates for genetic testing. The Amsterdam Criteria (see below) are useful, but do not identify up to 30% of potential Lynch syndrome carriers^{[citation needed]}. In colon cancer patients, pathologists can measure microsatellite instability in colon tumor specimens, which is a surrogate marker for DNA mismatch repair gene dysfunction. If there is microsatellite instability identified, there is a higher likelihood for a Lynch syndrome diagnosis. Recently, researchers combined microsatellite instability (MSI) profiling and immunohistochemistry testing for DNA mismatch repair gene expression and identified an extra 32% of Lynch syndrome carriers who would have been missed on MSI profiling alone.^{[citation needed]} Currently, this combined immunohistochemistry and MSI profiling strategy is the most advanced way of identifying candidates for genetic testing for the Lynch syndrome.

Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.

Amsterdam criteria

The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:^[25]

Amsterdam Criteria:

Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two
Two successive affected generations
One or more colon cancers diagnosed under age 50 years
Familial adenomatous polyposis (FAP) has been excluded

Amsterdam Criteria II:

Three or more family members with HNPCC-related cancers, one of whom is a first degree relative of the other two
Two successive affected generations
One or more of the HNPCC-related cancers diagnosed under age 50 years
Familial adenomatous polyposis (FAP) has been excluded

Diagnosis

The Amsterdam clinical criteria identifies candidates for genetic testing, and genetic testing can make a diagnosis of Lynch syndrome. Genetic testing is commercially available and consists of a blood test.

Treatment

Surgery remains the front-line therapy for HNPCC. There is an ongoing controversy over the benefit of 5-fluorouracil-based adjuvant therapies for HNPCC-related colorectal tumours, particularly those in stages I and II.^[26]

Prevention

After reporting a null finding from their randomized controlled trial of aspirin (ASA) to prevent against the colorectal neoplasia of Lynch Syndrome,^[27] Burn and colleagues have recently reported new data, representing a longer follow-up period than reported in the initial NEJM paper. These new data demonstrate a reduced incidence in Lynch Syndrome patients who were exposed to at least four years of high-dose aspirin, with a satisfactory risk profile.^[28] These results have been widely covered in the media; future studies will look at modifying (lowering) the dose (to reduce risk associated with the high dosage of ASA).

Epidemiology

In the United States, about 160,000 new cases of colorectal cancer are diagnosed each year. Hereditary nonpolyposis colorectal cancer is responsible for approximately 2 percent to 7 percent of all diagnosed cases of colorectal cancer. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome.^[29]

References

^ Kastrinos F, Mukherjee B, Tayob N, et al. (October 2009). "Risk of pancreatic cancer in families with Lynch syndrome". JAMA 302 (16): 1790–5. doi:10.1001/jama.2009.1529. PMID 19861671.
^ Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ (February 1966). "Hereditary factors in cancer. Study of two large midwestern kindreds". Arch. Intern. Med. 117 (2): 206–12. doi:10.1001/archinte.117.2.206. PMID 5901552.
^ Bellizzi AM, Frankel WL (2009). "Colorectal cancer due to deficiency in DNA mismatch repair function: a review". Advances in Anatomic Pathology 16 (6): 405–417. doi:10.1097/PAP.0b013e3181bb6bdc. PMID 19851131.
^ Lindor NM (October 2009). "Familial colorectal cancer type X: the other half of hereditary nonpolyposis colon cancer syndrome". Surg. Oncol. Clin. N. Am. 18 (4): 637–45. doi:10.1016/j.soc.2009.07.003. PMID 19793571.
^ Lindor NM, Rabe K, Petersen GM, et al. (April 2005). "Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X". JAMA 293 (16): 1979–85. doi:10.1001/jama.293.16.1979. PMC 2933042. PMID 15855431.
^ Scott RJ, McPhillips M, Meldrum CJ, et al. (January 2001). "Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds". Am. J. Hum. Genet. 68 (1): 118–127. doi:10.1086/316942. PMC 1234904. PMID 11112663.
^ Gologan A, Krasinskas A, Hunt J, Thull DL, Farkas L, Sepulveda AR (November 2005). "Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability". Arch. Pathol. Lab. Med. 129 (11): 1390–7. doi:10.1043/1543-2165(2005)129[1390:POTRBG]2.0.CO;2. PMID 16253017.
^ Umar A, Boland CR, Terdiman JP, et al. (February 2004). "Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability". J. Natl. Cancer Inst. 96 (4): 261–8. doi:10.1093/jnci/djh034. PMC 2933058. PMID 14970275.
^ Lipton LR, Johnson V, Cummings C, et al. (December 2004). "Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic". J. Clin. Oncol. 22 (24): 4934–43. doi:10.1200/JCO.2004.11.084. PMID 15611508.
^ Hereditary Colorectal Cancer > Background. From Medscape. By Juan Carlos Munoz and Louis R Lambiase. Updated: Oct 31, 2011
^ Lee, S. E.; Kang, S. Y.; Cho, J; Lee, B; Chang, D. K.; Woo, H; Kim, J. W.; Park, H. Y.; Do, I. G.; Kim, Y. E.; Kushima, R; Lauwers, G. Y.; Park, C. K.; Kim, K. M. (2014). "Pyloric Gland Adenoma in Lynch Syndrome". The American Journal of Surgical Pathology: 1. doi:10.1097/PAS.0000000000000185. PMID 24518125. edit
^ Hoffman, Barbara L. (2012). Williams Gynecology: Chapter 33, Endometrial Cancer (2nd ed.). New York: McGraw-Hill Medical. ISBN 978-0071716727.
^ Pathology of Hereditary Nonpolyposis Colorectal Cancer - JASS 910 (1): 62 - Annals of the New York Academy of Sciences
^ Oki, E.; Oda, S.; Maehara, Y.; Sugimachi, K. (1999). "Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair". Oncogene 18 (12): 2143–2147. doi:10.1038/sj.onc.1202583. PMID 10321739. edit
^ Fishel R, Lescoe M, Rao M, Copeland N, Jenkins N, Garber J, Kane M, Kolodner R (1993). "The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer". Cell 75 (5): 1027–38. doi:10.1016/0092-8674(93)90546-3. PMID 8252616.
^ Papadopoulos N, Nicolaides N, Wei Y, Ruben S, Carter K, Rosen C, Haseltine W, Fleischmann R, Fraser C, Adams M (1994). "Mutation of a mutL homolog in hereditary colon cancer". Science 263 (5153): 1625–9. doi:10.1126/science.8128251. PMID 8128251.
^ Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, Igari T, Koike M, Chiba M, Mori T. (1997). "Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer". Nature Genetics 17 (3): 271–2. doi:10.1038/ng1197-271. PMID 9354786.
^ Thompson E, Meldrum CJ, Crooks R, et al. (March 2004). "Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations". Clin. Genet. 65 (3): 215–25. doi:10.1111/j.1399-0004.2004.00214.x. PMID 14756672.
^ Nicolaides NC, Papadopoulos N, Liu B, et al. (September 1994). "Mutations of two PMS homologues in hereditary nonpolyposis colon cancer". Nature 371 (6492): 75–80. doi:10.1038/371075a0. PMID 8072530.
^ Lu SL, Kawabata M, Imamura T, et al. (May 1998). "HNPCC associated with germline mutation in the TGF-beta type II receptor gene". Nat. Genet. 19 (1): 17–8. doi:10.1038/ng0598-17. PMID 9590282.
^ Ou J, Rasmussen M, Westers H, et al. (April 2009). "Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome". Genes Chromosomes Cancer 48 (4): 340–50. doi:10.1002/gcc.20644. PMID 19156873.
^ Ramsoekh D, Wagner A, van Leerdam ME, et al. (November 2008). "A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting". Gut 57 (11): 1539–44. doi:10.1136/gut.2008.156695. PMID 18625694.
^ Suchy J, Lubinski J (2008). "MSH6 syndrome". Hered Cancer Clin Pract 6 (2): 103–104. doi:10.1186/1897-4287-6-2-103. PMC 2735474. PMID 19804606.
^ Goldberg Y, Porat RM, Kedar I, et al. (October 2009). "An Ashkenazi founder mutation in the MSH6 gene leading to HNPCC". Fam. Cancer 9 (2): 141–50. doi:10.1007/s10689-009-9298-9. ISBN 68900992989 Check |isbn= value (help). PMID 19851887.
^ Vasen HF, Watson P, Mecklin JP, Lynch HT (June 1999). "New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC". Gastroenterology 116 (6): 1453–6. doi:10.1016/S0016-5085(99)70510-X. PMID 10348829.
^ Boland CR, Koi M, Chang DK, Carethers JM. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch Syndrome: from bench to bedside. Familial Cancer epub 2007; doi:10.1007/s10689-007-9145-9
^ Burn J, Bishop DT, Mecklin JP, et al. (December 2008). "Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome". N. Engl. J. Med. 359 (24): 2567–78. doi:10.1056/NEJMoa0801297. PMID 19073976.
^ "Aspirin Confers Long-Term Protective Effect in Lynch Syndrome Patients". Retrieved 2009-11-07.
^ Cancer Information, Research, and Treatment for all Types of Cancer | OncoLink

External links

FAQs on HNPCC from the National Institute of Health
GeneReviews/NCBI/NIH/UW entry on Lynch syndrome
hnpcc at NIH/UW GeneTests
National Cancer Institute: Genetics of Colorectal Cancer information summary
Lynch Syndrome Patient and Professional Information Website
Hereditary Colorectal Cancer Syndromes
Hereditary colorectal cancer information
Cancer.Net: Lynch Syndrome
http://www.ihavelynchsyndrome.com [1]

UpToDate Contents

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1. リンチ症候群（遺伝性非ポリポーシス大腸癌）：臨床的特徴および診断 lynch syndrome hereditary nonpolyposis colorectal cancer clinical manifestations and diagnosis
2. リンチ症候群（遺伝性非ポリポーシス性大腸癌）：スクリーニングおよびマネージメント lynch syndrome hereditary nonpolyposis colorectal cancer screening and management
3. ミュアト－ル症候群 muir torre syndrome
4. リンチ症候群（遺伝性非ポリポーシス性大腸癌）の女性における子宮体癌および卵巣癌のスクリーニングおよび予防 endometrial and ovarian cancer screening and prevention in women with lynch syndrome hereditary nonpolyposis colorectal cancer
5. 大腸がんの家族歴を有する患者における大腸癌スクリーニング screening for colorectal cancer in patients with a family history of colorectal cancer

English Journal

Lynch syndrome: a pediatric perspective.

Huang SC1, Durno CA, Erdman SH.Author information 1*Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California, San Diego †Department of Pediatrics, Division of Gastroenterology/Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Canada ‡Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH.AbstractColorectal cancer is a rare disease in the pediatric age group and, when present, suggests an underlying genetic predisposition. The most common hereditary colon cancer susceptibility condition, Lynch syndrome (LS), previously known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant condition caused by a germline mutation in 1 of 4 DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. The mutation-prone phenotype of this disorder is associated with gastrointestinal, endometrial, and other cancers and is now being identified in both symptomatic adolescents with malignancy as well in asymptomatic mutation carriers who are at risk for a spectrum of gastrointestinal and other cancers later in life. We review the DNA MMR system, our present understanding of LS in the pediatric population, and discuss the newly identified biallelic form of the disease known as constitutional mismatch repair deficiency syndrome. Both family history and tumor characteristics can help to identify patients who should undergo genetic testing for these cancer predisposition syndromes. Patients who carry either single allele (LS) or double allele (constitutional mismatch repair deficiency syndrome) mutations in the MMR genes benefit from cancer surveillance programs that target both the digestive and extraintestinal cancer risk of these diseases. Because spontaneous mutation in any one of the MMR genes is extremely rare, genetic counseling and testing are suggested for all at-risk family members.
Journal of pediatric gastroenterology and nutrition.J Pediatr Gastroenterol Nutr.2014 Feb;58(2):146-54. doi: 10.1097/MPG.0000000000000179.
Colorectal cancer is a rare disease in the pediatric age group and, when present, suggests an underlying genetic predisposition. The most common hereditary colon cancer susceptibility condition, Lynch syndrome (LS), previously known as hereditary nonpolyposis colorectal cancer, is an autosomal domin
PMID 24051481

Lynch syndrome presenting as endometrial cancer.

Tafe LJ1, Riggs ER, Tsongalis GJ.Author information 1Departments of Pathology and.AbstractBACKGROUND: Lynch syndrome (LS) is the most common form of the hereditary colon cancer syndromes. Because of its high prevalence, a nationwide campaign has begun to screen all colorectal cancers for the genetic abnormalities associated with LS.
Clinical chemistry.Clin Chem.2014 Jan;60(1):111-21. doi: 10.1373/clinchem.2013.206888. Epub 2013 Nov 5.
BACKGROUND: Lynch syndrome (LS) is the most common form of the hereditary colon cancer syndromes. Because of its high prevalence, a nationwide campaign has begun to screen all colorectal cancers for the genetic abnormalities associated with LS.CONTENT: Next to colorectal cancer, endometrial cancer i
PMID 24193118

Metachronous serrated neoplasia is uncommon after right colectomy in patients with methylator colon cancers with a high degree of microsatellite instability.

Messick CA1, Kravochuck S, Church JM, Kalady MF.Author information 11Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 2Sanford R. Weiss, M.D., Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, Ohio 3Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.AbstractBACKGROUND: Right-sided serrated polyps are precursors to sporadic microsatellite unstable colon cancers via the methylator pathway and have a high rate of synchronous and metachronous lesions. Serrated polyps also occur in Lynch syndrome, where right-sided microsatellite unstable cancers arise from germline mutations in mismatch repair genes.
Diseases of the colon and rectum.Dis Colon Rectum.2014 Jan;57(1):39-46. doi: 10.1097/01.dcr.0000437690.18709.76.
BACKGROUND: Right-sided serrated polyps are precursors to sporadic microsatellite unstable colon cancers via the methylator pathway and have a high rate of synchronous and metachronous lesions. Serrated polyps also occur in Lynch syndrome, where right-sided microsatellite unstable cancers arise from
PMID 24316944

Japanese Journal

1) ゲノム不安定性・遺伝子変異に基づく子宮体癌の浸潤能獲得と分子生物学的予後不良因子の検討(シンポジウム1:腫瘍「婦人科癌の浸潤・転移機構の解明と臨床応用」,第65回日本産科婦人科学会・学術講演会講演要旨)

日本産科婦人科學會雜誌 65(10), 2388-2401, 2013-10-01
NAID 110009674401

遺伝性非ポリポーシス大腸癌に異時性両側上部尿路癌と膀胱癌を合併した1例

泌尿器科紀要 57(10), 559-563, 2011-10
NAID 40019038780

肛門側ほど癌化傾向を示した同時性多発大腸腫瘍の1例

日本外科系連合学会誌 35(4), 621-626, 2010-08-30
NAID 10027657940

Related Pictures

★リンクテーブル★

リンク元	「癌」「Lynch syndrome」「HNPCC」
関連記事	「hereditary」「nonpolyposis」「cancer」「colon」

「癌」

Hereditary nonpolyposis colorectal cancer
	Classification and external resources
	Micrograph showing tumor-infiltrating lymphocytes (in a colorectal cancer), a finding associated with MSI-H tumours, as may be seen in Lynch syndrome. H&E stain.
ICD-10	C18-C20
ICD-9	153.0-154.1
OMIM	120435 609310 114400
DiseasesDB	5812
MeSH	D003123

　　[★]

英: cancer
関: 悪性腫瘍

種類

癌腫(carcinoma):上皮性
肉腫(sarcoma):間葉系
carcinoma：腺癌(adenocarcinma)、扁平上皮癌(squamous cell carcinoma)、移行上皮癌(transitional cell carcinoma)
sarcoma：骨肉腫、横紋筋肉腫、平滑筋肉腫、脂肪肉腫、線維肉腫

Neoplasm	Causes	Effect
Small cell lung carcinoma	ACTH or ACTH-like peptide	Cushing’s syndrome
Small cell lung carcinoma and intracranial neoplasms	ADH	SIADH
Squamous cell lung carcinoma, renal cell carcinoma, breast carcinoma, multiple myeloma, and bone metastasis (lysed bone)	PTH-related peptide, TGF-β, TNF-α, IL-1	Hypercalcemia
Renal cell carcinoma, hemangioblastoma	Erythropoietin	Polycythemia
Thymoma, small cell lung carcinoma	Antibodies against presynaptic Ca2+ channels at neuromuscular junction	Lambert-Eaton syndrome (muscle weakness)
Leukemias and lymphomas	Hyperuricemia due to excess nucleic acid turnover (i.e., cytotoxic therapy)	Gout, urate nephropathy

最新癌統計

http://ganjoho.ncc.go.jp/public/statistics/pub/statistics01.html

●2005年の死亡数が多い部位は順に
	1位	2位	3位	4位	5位
男性	肺	胃	肝臓	結腸	膵臓	結腸と直腸を合わせた大腸は4位
女性	胃	肺	結腸	肝臓	乳房	結腸と直腸を合わせた大腸は1位
男女計	肺	胃	肝臓	結腸	膵臓	結腸と直腸を合わせた大腸は3位

●2001年の罹患数が多い部位は順に
	1位	2位	3位	4位	5位
男性	胃	肺	結腸	肝臓	前立腺	結腸と直腸を合わせた大腸は2位
女性	乳房*1	胃	結腸	子宮*1	肺	結腸と直腸を合わせた大腸は1位
男女計	胃	肺	結腸	乳房*1	肝臓	結腸と直腸を合わせた大腸は2位
*1上皮内がんを含む。

癌の素因となる遺伝子

HIM.494

Table 79-1 Cancer Predisposition Syndromes and Associated Genes
Syndrome	Gene	Chromosome	Inheritance	Tumors
ataxia telangiectasia	ATM	11q22-q23	AR	breast cancer
autoimmune lymphoproliferative syndrome	FAS	10q24	AD	lymphomas
autoimmune lymphoproliferative syndrome	FASL	1q23		lymphomas
Bloom syndrome	BLM	15q26.1	AR	cancer of all types
Cowden syndrome	PTEN	10q23	AD	breast, thyroid
familial adenomatous polyposis	APC	5q21	AD	intestinal adenoma, colorectal cancer
familial melanoma	p16INK4	9p21	AD	melanoma, pancreatic cancer
familial Wilms tumor	WT1	11p13	AD	pediatric kidney cancer
hereditary breast/ovarian cancer	BRCA1	17q21	AD	breast, ovarian, colon, prostate
hereditary breast/ovarian cancer	BRCA2	13q12.3		breast, ovarian, colon, prostate
hereditary diffuse gastric cancer	CDH1	16q22	AD	stomach cancers
hereditary multiple exostoses	EXT1	8q24	AD	exostoses, chondrosarcoma
hereditary multiple exostoses	EXT2	11p11-12		exostoses, chondrosarcoma
hereditary prostate cancer	HPC1	1q24-25	AD	prostate carcinoma
hereditary retinoblastoma	RB1	13q14.2	AD	retinoblastoma, osteosarcoma
hereditary nonpolyposis colon cancer (HNPCC)	MSH2	2p16	AD	colon, endometrial, ovarian, stomach, small bowel, ureter carcinoma
	MLH1	3p21.3
	MSH6	2p16
	PMS2	7p22
hereditary papillary renal carcinoma	MET	7q31	AD	papillary renal tumor
juvenile polyposis	SMAD4	18q21	AD	gastrointestinal, pancreatic cancers
Li-Fraumeni	TP53	17p13.1	AD	sarcoma, breast cancer
multiple endocrine neoplasia type 1	MEN1	11q13	AD	parathyroid, endocrine, pancreas, and pituitary
multiple endocrine neoplasia type 2a	RET	10q11.2	AD	medullary thyroid carcinoma, pheochromocytoma
neurofibromatosis type 1	NF1	17q11.2	AD	neurofibroma, neurofibrosarcoma, brain tumor
neurofibromatosis type 2	NF2	22q12.2	AD	vestibular schwannoma, meningioma, spine
nevoid basal cell carcinoma syndrome (Gorlin's syndrome)	PTCH	9q22.3	AD	basal cell carcinoma, medulloblastoma, jaw cysts
tuberous sclerosis	TSC1	9q34	AD	angiofibroma, renal angiomyolipoma
tuberous sclerosis	TSC2	16p13.3		angiofibroma, renal angiomyolipoma
von Hippel–Lindau	VHL	3p25-26	AD	kidney, cerebellum, pheochromocytoma

癌遺伝子、癌抑制遺伝子

癌の危険因子

生活習慣病#生活習慣病などのリスクファクターを改変

疾患		危険因子	防御因子
悪性腫瘍	胃癌	塩辛い食品、喫煙、くん製製品、ニトロソアミン土壌、腸上皮化生、Helicobacter pyroli	ビタミンC、野菜、果実
	食道癌	喫煙、飲酒、熱い飲食物	野菜、果実
	結腸癌	高脂肪食、肉食、低い身体活動、腸内細菌叢の変化、遺伝(家族性大腸腺腫症)
	肝癌	HBVキャリア・HCVキャリア、アフラトキシン、住血吸虫、飲酒
	肺癌	喫煙(特に扁平上皮癌)、大気汚染、職業的暴露(石綿(扁平上皮癌、悪性中皮腫)、クロム)	野菜、果実
	膵癌	高脂肪食、喫煙
	口腔癌	喫煙(口唇・舌-パイプ)、ビンロウ樹の実(口腔、舌)、飲酒
	咽頭癌	EBウイルス(上咽頭癌)、飲酒
	喉頭癌	喫煙、男性、アルコール
	乳癌	高年初産、乳癌の家族歴、肥満、未婚で妊娠回数少ない、無授乳、脂肪の過剰摂取、低年齢初経、高年齢閉経	母乳授乳
	子宮頚癌	初交年齢若い、早婚、多産、性交回数が多い(売春)、貧困、不潔]、HSV-2、HPV、流産、人工妊娠中絶回数が多い
	子宮体癌	肥満、糖尿病、ピル、エストロゲン常用、未婚、妊娠回数少ない、乳癌後のタモキシフエン内服
	膀胱癌	喫煙、鎮痛剤乱用、ビルハルツ住血吸虫、サッカリン、防腐剤
	皮膚癌	日光(紫外線)、ヒ素(Bowen病)
	白血病	放射線、ベンゼン、地域集積性(ATL)、ダウン症(小児白血病)
	骨腫瘍	電離放射線
	甲状腺癌	ヨード欠乏または過剰

「Lynch syndrome」

　　[★] 遺伝性非ポリポーシス大腸癌, hereditary nonpolyposis colon cancer。リンチ症候群

「HNPCC」

　　[★] 遺伝性非ポリポーシス大腸癌 hereditary nonpolyposis colon cancer

「hereditary」

　　[★]

adj.

遺伝性の、遺伝の

関: heredity、heritable、inherit、inheritable、inheritable character、inheritance、inherited

「nonpolyposis」

　　[★]

非・リープ性、非・リ・ーシス

「cancer」

　　[★]

同: 癌腫
関: tumor

「colon」

　　[★] 結腸　　　　　　

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[pmid5901552-2] Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ (February 1966). "Hereditary factors in cancer. Study of two large midwestern kindreds". Arch. Intern. Med. 117 (2): 206–12. doi:10.1001/archinte.117.2.206. PMID 5901552.

[bellizzi-3] Bellizzi AM, Frankel WL (2009). "Colorectal cancer due to deficiency in DNA mismatch repair function: a review". Advances in Anatomic Pathology 16 (6): 405–417. doi:10.1097/PAP.0b013e3181bb6bdc. PMID 19851131.

[pmid19793571-4] Lindor NM (October 2009). "Familial colorectal cancer type X: the other half of hereditary nonpolyposis colon cancer syndrome". Surg. Oncol. Clin. N. Am. 18 (4): 637–45. doi:10.1016/j.soc.2009.07.003. PMID 19793571.

[pmid15855431-5] Lindor NM, Rabe K, Petersen GM, et al. (April 2005). "Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X". JAMA 293 (16): 1979–85. doi:10.1001/jama.293.16.1979. PMC 2933042. PMID 15855431.

[pmid11112663-6] Scott RJ, McPhillips M, Meldrum CJ, et al. (January 2001). "Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds". Am. J. Hum. Genet. 68 (1): 118–127. doi:10.1086/316942. PMC 1234904. PMID 11112663.

[pmid16253017-7] Gologan A, Krasinskas A, Hunt J, Thull DL, Farkas L, Sepulveda AR (November 2005). "Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability". Arch. Pathol. Lab. Med. 129 (11): 1390–7. doi:10.1043/1543-2165(2005)129[1390:POTRBG]2.0.CO;2. PMID 16253017.

[pmid14970275-8] Umar A, Boland CR, Terdiman JP, et al. (February 2004). "Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability". J. Natl. Cancer Inst. 96 (4): 261–8. doi:10.1093/jnci/djh034. PMC 2933058. PMID 14970275.

[pmid15611508-9] Lipton LR, Johnson V, Cummings C, et al. (December 2004). "Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic". J. Clin. Oncol. 22 (24): 4934–43. doi:10.1200/JCO.2004.11.084. PMID 15611508.

[10] Hereditary Colorectal Cancer > Background. From Medscape. By Juan Carlos Munoz and Louis R Lambiase. Updated: Oct 31, 2011

[11] Lee, S. E.; Kang, S. Y.; Cho, J; Lee, B; Chang, D. K.; Woo, H; Kim, J. W.; Park, H. Y.; Do, I. G.; Kim, Y. E.; Kushima, R; Lauwers, G. Y.; Park, C. K.; Kim, K. M. (2014). "Pyloric Gland Adenoma in Lynch Syndrome". The American Journal of Surgical Pathology: 1. doi:10.1097/PAS.0000000000000185. PMID 24518125. edit

[12] Hoffman, Barbara L. (2012). Williams Gynecology: Chapter 33, Endometrial Cancer (2nd ed.). New York: McGraw-Hill Medical. ISBN 978-0071716727.

[13] Pathology of Hereditary Nonpolyposis Colorectal Cancer - JASS 910 (1): 62 - Annals of the New York Academy of Sciences

[14] Oki, E.; Oda, S.; Maehara, Y.; Sugimachi, K. (1999). "Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair". Oncogene 18 (12): 2143–2147. doi:10.1038/sj.onc.1202583. PMID 10321739. edit

[15] Fishel R, Lescoe M, Rao M, Copeland N, Jenkins N, Garber J, Kane M, Kolodner R (1993). "The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer". Cell 75 (5): 1027–38. doi:10.1016/0092-8674(93)90546-3. PMID 8252616.

[16] Papadopoulos N, Nicolaides N, Wei Y, Ruben S, Carter K, Rosen C, Haseltine W, Fleischmann R, Fraser C, Adams M (1994). "Mutation of a mutL homolog in hereditary colon cancer". Science 263 (5153): 1625–9. doi:10.1126/science.8128251. PMID 8128251.

[17] Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, Igari T, Koike M, Chiba M, Mori T. (1997). "Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer". Nature Genetics 17 (3): 271–2. doi:10.1038/ng1197-271. PMID 9354786.

[pmid14756672-18] Thompson E, Meldrum CJ, Crooks R, et al. (March 2004). "Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations". Clin. Genet. 65 (3): 215–25. doi:10.1111/j.1399-0004.2004.00214.x. PMID 14756672.

[pmid8072530-19] Nicolaides NC, Papadopoulos N, Liu B, et al. (September 1994). "Mutations of two PMS homologues in hereditary nonpolyposis colon cancer". Nature 371 (6492): 75–80. doi:10.1038/371075a0. PMID 8072530.

[pmid9590282-20] Lu SL, Kawabata M, Imamura T, et al. (May 1998). "HNPCC associated with germline mutation in the TGF-beta type II receptor gene". Nat. Genet. 19 (1): 17–8. doi:10.1038/ng0598-17. PMID 9590282.

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[pmid18625694-22] Ramsoekh D, Wagner A, van Leerdam ME, et al. (November 2008). "A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting". Gut 57 (11): 1539–44. doi:10.1136/gut.2008.156695. PMID 18625694.

[pmid19804606-23] Suchy J, Lubinski J (2008). "MSH6 syndrome". Hered Cancer Clin Pract 6 (2): 103–104. doi:10.1186/1897-4287-6-2-103. PMC 2735474. PMID 19804606.

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[25] Vasen HF, Watson P, Mecklin JP, Lynch HT (June 1999). "New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC". Gastroenterology 116 (6): 1453–6. doi:10.1016/S0016-5085(99)70510-X. PMID 10348829.

[26] Boland CR, Koi M, Chang DK, Carethers JM. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch Syndrome: from bench to bedside. Familial Cancer epub 2007; doi:10.1007/s10689-007-9145-9

[pmid19073976-27] Burn J, Bishop DT, Mecklin JP, et al. (December 2008). "Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome". N. Engl. J. Med. 359 (24): 2567–78. doi:10.1056/NEJMoa0801297. PMID 19073976.

[28] "Aspirin Confers Long-Term Protective Effect in Lynch Syndrome Patients". Retrieved 2009-11-07.

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Hereditary nonpolyposis colorectal cancer
Classification and external resources
Micrograph showing tumor-infiltrating lymphocytes (in a colorectal cancer), a finding associated with MSI-H tumours, as may be seen in Lynch syndrome. H&E stain.
ICD-10	C18-C20
ICD-9	153.0-154.1
OMIM	120435 609310 114400
DiseasesDB	5812
MeSH	D003123

匿名

検索

案内

hereditary nonpolyposis colon cancer