832:(MMR) protein expression in tumours that are associated with Lynch syndrome. While it is not diagnostic of a Lynch syndrome, it can play a role in identifying people who should have germline testing. Two methods of implementation of IHC testing includes age-based testing and universal testing for all people. Currently, there is no widespread agreement regarding which screening method should be used. Age-based testing for IHC has been suggested in part due to cost-benefit analyses, whereas universal testing for all people with colorectal cancer ensures people with Lynch Syndrome are not missed. To address the costs, researchers are trying to predict MSI or IHC directly from the way the tumor looks under the microscope, without doing any molecular testing.
32:
75:
501:
781:. Therefore, families found to have a deleterious mutation in a Lynch syndrome gene should be considered to have Lynch syndrome regardless of the extent of the family history. This also means that the Amsterdam criteria fail to identify many people who are 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.
785:
new generation, without inheriting the gene. These people 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. It is also important to note, that deleterious mutation in one of MMR genes alone is not sufficient to cause cancer, but that rather further mutations in other tumour suppressor genes need to occur.
1201:, characterized the syndrome in 1966. In his earlier work, he described the disease entity as "cancer family syndrome." The term "Lynch syndrome" was coined in 1984 by other authors; Lynch named the condition HNPCC in 1985. Since then the two terms have been used interchangeably, until later advances in the understanding of the genetics of the disease led to the term HNPCC falling out of favor.
784:
Most people with Lynch syndrome inherit the condition from a parent. However, due to incomplete penetrance, variable age of cancer diagnosis, cancer risk reduction, or early death, not all people with an Lynch syndrome gene mutation have a parent who had cancer. Some people develop HNPCC de-novo in a
1212:
are met but there is no known DNA mismatch repair defect. 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. About 35% of people who meet
Amsterdam criteria do not
1055:
The
Bethesda criteria were developed in 1997 and later updated in 2004 by the National Cancer Institute to identify persons requiring further testing for Lynch syndrome through MSI. In contrast to the Amsterdam Criteria, the Revised Bethesda Guidelines use pathological data in addition to clinical
574:
The impairment of either gene for the protein dimer impairs the protein function. These 4 genes are involved in error correction (mismatch repair), so dysfunction of the genes can lead to the inability to fix DNA replication errors and cause Lynch syndrome. Lynch syndrome is known to be associated
773:
mutations are more likely to be
Amsterdam criteria II-negative. The presentation with MSH6 is slightly different from with MLH1 and MSH2, and the term "MSH6 syndrome" has been used to describe this condition. In one study, the Bethesda guidelines were more sensitive than the Amsterdam Criteria in
3154:
Stjepanovic N, Moreira L, Carneiro F, Balaguer F, Cervantes A, Balmaña J, Martinelli E; ESMO Guidelines
Committee. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow- up†. Ann Oncol. 2019 Oct 1;30(10):1558-1571. doi: 10.1093/annonc/mdz233.
1186:. Lynch syndrome-causing mutations are found in approximately 3% of all diagnosed colorectal cancers, and 1.8% of all diagnosed endometrial cancers. 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.
3271:
André, Thierry; Shiu, Kai-Keen; Kim, Tae Won; Jensen, Benny
Vittrup; Jensen, Lars Henrik; Punt, Cornelis; Smith, Denis; Garcia-Carbonero, Rocio; Benavides, Manuel; Gibbs, Peter; de la Fouchardiere, Christelle; Rivera, Fernando; Elez, Elena; Bendell, Johanna; Le, Dung T.; Yoshino, Takayuki; Van
1169:
Though the exact prevalence of Lynch syndrome-causing mutations in the general population remain unknown, recent studies estimate the prevalence to be 1 in 279 individuals, or 0.35%. Certain populations are known to have a higher prevalence of founder mutations, including, but not limited to,
935:
are recommended as a preventative method of surveillance for individuals who have Lynch syndrome, or LS-associated genes. Specifically, it is recommended that colonoscopies begin at ages 20–25 for MLH1 and MSH2 mutation carriers and 35 years for MSH6 and PMS2 mutation carriers. Colonoscopic
817:(MSI) testing. In the US, professional societies recommend testing every colon cancer for MSI or IHC as screening for Lynch syndrome, but this is not always performed because of cost and resource limitations. Genetic testing is commercially available and consists of a blood test.
1129:
or total colectomy with ileorectal anastomosis. Due to increased risk of colorectal cancer following partial colectomy and similar quality of life after both surgeries, a total colectomy may be a preferred treatment for Lynch syndrome, especially in younger patients.
952:
is recommended annually for ovarian and endometrial cancer screening. For women with Lynch syndrome, a yearly CA-125 blood test can be used to screen for ovarian cancer, however there is limited data on the efficacy of this test in reducing mortality.
2393:
Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, et al. (August 2014). "Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer".
275:
diagnosis is 44 for members of families that meet the
Amsterdam criteria. 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
1493:
Sobocińska, Joanna; Kolenda, Tomasz; Teresiak, Anna; Badziąg-Leśniak, Natalia; Kopczyńska, Magda; Guglas, Kacper; Przybyła, Anna; Filas, Violetta; Bogajewska-Ryłko, Elżbieta; Lamperska, Katarzyna; Mackiewicz, Andrzej (2020-10-05).
961:
There are also strategies for detecting other cancers early or reducing the chances of developing them that people with Lynch syndrome can discuss with their doctor, however their effectiveness is not clear. These options include:
284:
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.
2774:"Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)"
1071:
Presence of synchronous or metachronous colorectal or other Lynch syndrome associated cancers (e.g. cancers of endometrium, ovary, stomach, small bowel, pancreas, biliary tract, ureter, renal pelvis, brain, sebaceous glands,
2234:
Ramsoekh D, Wagner A, van
Leerdam ME, Dinjens WN, Steyerberg EW, Halley DJ, et al. (November 2008). "A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting".
861:, suggesting that tumor-infiltrating lymphocytes might be a good option for therapy for these patients. High numbers of tumor-infiltrating lymphocytes were related with better survival rates and treatment responses.
856:
analysis of microsatellite regions. MSI analysis can be used to identify people who may have Lynch syndrome and direct them for further testing. One study noted that one third of MSI colorectal cancers showed a low
3998:
3979:
2372:
1553:
Møller, Pål; Seppälä, Toni T.; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paulo; Gareth Evans, D.; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf H.; Jeffries, Jacqueline (2018).
2955:
Vasen, Hans F A; Blanco, Ignacio; Aktan-Collan, Katja; Gopie, Jessica P; Alonso, Angel; Aretz, Stefan; Bernstein, Inge; Bertario, Lucio; Burn, John; Capella, Gabriel; Colas, Chrystelle (June 2013).
4726:
280:, making endometrial cancer the most common sentinel cancer in Lynch syndrome. The most common symptom of endometrial cancer is abnormal vaginal bleeding. In HNPCC, the mean age of diagnosis of
288:
Significant variation in the rate of cancer has been found depending on the mutation involved. Up to the age of 75 years the risks of different cancers by the mutations are in the table below.
1387:
Vogel JD, Eskicioglu C, Weiser MR, Feingold DL, Steele SR (October 2017). "The
American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer".
2034:
Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, et al. (November 1997). "Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer".
848:). MSI is associated with alternate sized repetitive DNA sequences that are not present in the correlated germ line DNA resulting in 15-20% of colorectal cancers. MSI is identified through
1089:
It is important to note that these clinical criteria can be difficult to use in practice and clinical criteria used alone misses between 12 and 68 percent of Lynch syndrome cases.
1828:
Tamura K, Kaneda M, Futagawa M, Takeshita M, Kim S, Nakama M, et al. (September 2019). "Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome".
2080:
Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, et al. (September 1994). "Mutations of two PMS homologues in hereditary nonpolyposis colon cancer".
4719:
2131:
Lu SL, Kawabata M, Imamura T, Akiyama Y, Nomizu T, Miyazono K, Yuasa Y (May 1998). "HNPCC associated with germline mutation in the TGF-beta type II receptor gene".
4972:
840:
Mutations in DNA mismatch repair systems can lead to difficulty transmitting regions within the DNA which contain repeating patterns of two or three nucleotides (
4992:
4712:
3815:"Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic"
1085:
Person with colorectal cancer and two or more first- or second-degree relatives with colorectal cancer or Lynch syndrome associated cancer diagnosed at any age.
1082:
Colorectal cancer diagnosed in a person with one or more first-degree relative with colorectal cancer or Lynch syndrome associated tumour diagnosed under age 50
2329:
Goldberg Y, Porat RM, Kedar I, Shochat C, Galinsky D, Hamburger T, et al. (June 2010). "An
Ashkenazi founder mutation in the MSH6 gene leading to HNPCC".
1005:
Amsterdam I Criteria (all bullet points must be fulfilled): The
Amsterdam I criteria were published in 1990; however, were felt to be insufficiently sensitive.
232:
In addition to the types of cancer found in the chart above, it is understood that Lynch syndrome also contributes to an increased risk of small bowel cancer,
1010:
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
2376:
4163:
1125:
Surgery remains the front-line therapy for Lynch syndrome. Patients with Lynch syndrome who develop colorectal cancer may be treated with either a partial
3478:
1991:
Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, et al. (March 1994). "Mutation of a mutL homolog in hereditary colon cancer".
3014:"New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC"
4102:
3175:"The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside"
2436:"Artificial Intelligence for Histology-Based Detection of Microsatellite Instability and Prediction of Response to Immunotherapy in Colorectal Cancer"
1744:"Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review"
3678:"Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds"
3346:
1703:"Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair"
1555:"Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database"
1153:
In 2024 development for a vaccine called LynchVax that would reduce the risk of cancer from the disease has been started by scientist from the
1145:
Checkpoint blockade with anti-PD-1 therapy is now preferred first line therapy for advanced Microsatellite-Instability–High colorectal cancer.
3500:
Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ (February 1966). "Hereditary factors in cancer. Study of two large midwestern kindreds".
3727:"Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability"
4394:
3726:
551:
MLH1 protein dimerizes with PMS2 protein to form MutLα, which coordinates the binding of other proteins involved with mismatch repair like
150:
4270:
1026:
The Amsterdam II criteria were developed in 1999 and improved the diagnostic sensitivity for Lynch syndrome by including cancers of the
2824:
Ring KL, Garcia C, Thomas MH, Modesitt SC (November 2017). "Current and future role of genetic screening in gynecologic malignancies".
3814:
1952:"Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders"
1685:
1423:
4156:
4644:
3062:
Vindigni SM, Kaz AM (April 2016). "Universal Screening of Colorectal Cancers for Lynch Syndrome: Challenges and Opportunities".
924:
and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.
805:
gene, identified by genetic testing. Candidates for germline genetic testing can be identified by clinical criteria such as the
4504:
3629:"Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X"
2555:
2499:
3938:
4189:
3766:"Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability"
3535:
Bellizzi AM, Frankel WL (November 2009). "Colorectal cancer due to deficiency in DNA mismatch repair function: a review".
2957:"Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts"
4693:
4649:
4149:
4017:
1198:
4704:
1435:
1683:
Pathology of Hereditary Nonpolyposis Colorectal Cancer - JASS 910 (1): 62 - Annals of the New York Academy of Sciences
1496:"Diagnostics of Mutations in MMR/EPCAM Genes and Their Role in the Treatment and Care of Patients with Lynch Syndrome"
1228:, AliveAndKickn, Lynch Syndrome UK and Bowel Cancer UK. In the US, National Lynch Syndrome Awareness Day is March 22.
4256:
802:
623:
450:
4767:
2176:"Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome"
1915:
Yurgelun MB, Hampel H (May 2018). "Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention".
4947:
4821:
4552:
2551:"Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation"
4136:
2708:
Taieb, Julien; Svrcek, Magali; Cohen, Romain; Basile, Debora; Tougeron, David; Phelip, Jean-Marc (November 2022).
4870:
556:
1137:-based adjuvant therapies for Lynch syndrome-related colorectal tumours, particularly those in stages I and II.
1039:
Three or more family members with HNPCC-related cancers, one of whom is a first-degree relative of the other two
4987:
4743:
4654:
4457:
4414:
4385:
3877:
1048:
1019:
43:
4926:
4365:
4126:
2925:
2867:
Sroczynski G, Gogollari A, Conrads-Frank A, Hallsson LR, Pashayan N, Widschwendter M, Siebert U (July 2020).
2607:"Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer"
1917:
American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting
2869:"Cost-Effectiveness of Early Detection and Prevention Strategies for Endometrial Cancer-A Systematic Review"
1216:
Complicating matters is the presence of an alternative set of criteria, known as the "Bethesda Guidelines."
1001:
The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:
4683:
4357:
4180:
4110:
1225:
985:
4115:
4099:
4982:
4735:
4623:
4399:
4375:
3272:
Cutsem, Eric; Yang, Ping; Farooqui, Mohammed Z.H.; Marinello, Patricia; Diaz, Luis A. (3 December 2020).
2710:"Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment"
4085:
3579:
4977:
4893:
4848:
4809:
4639:
4380:
4361:
4234:
887:
870:
845:
814:
521:
51:
31:
4121:
3676:
Scott RJ, McPhillips M, Meldrum CJ, Fitzgerald PE, Adams K, Spigelman AD, et al. (January 2001).
2434:
Hildebrand, Lindsey A.; Pierce, Colin J.; Dennis, Michael; Paracha, Munizay; Maoz, Asaf (2021-01-21).
2203:
4888:
4547:
4476:
4172:
3813:
Lipton LR, Johnson V, Cummings C, Fisher S, Risby P, Eftekhar Sadat AT, et al. (December 2004).
3764:
Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, RĂĽschoff J, et al. (February 2004).
1793:
Peltomäki P (March 2003). "Role of DNA mismatch repair defects in the pathogenesis of human cancer".
853:
252:
has also been associated with Lynch syndrome, although this relationship is not entirely understood.
3580:"Familial colorectal cancer type X: the other half of hereditary nonpolyposis colon cancer syndrome"
1250:"Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer"
4942:
4499:
4353:
4130:
4034:
1876:"The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer"
1742:
Yokoyama T, Takehara K, Sugimoto N, Kaneko K, Fujimoto E, Okazawa-Sakai M, et al. (May 2018).
1117:
to prevent cancer from developing) can be performed before ovarian or endometrial cancer develops.
74:
2175:
4865:
4688:
4437:
4206:
2549:
Snowsill T, Coelho H, Huxley N, Jones-Hughes T, Briscoe S, Frayling IM, Hyde C (September 2017).
2493:
Snowsill T, Huxley N, Hoyle M, Jones-Hughes T, Coelho H, Cooper C, et al. (September 2014).
945:
119:
3842:
4788:
4529:
4317:
4279:
971:
3112:
Bui QM, Lin D, Ho W (February 2017). "Approach to Lynch Syndrome for the Gastroenterologist".
1064:
If a person meets any 1 of 5 criteria the tumour(s) from the person should be tested for MSI:
4831:
4389:
1874:
Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, et al. (December 1993).
1102:
974:
cancer every 3–5 years, starting at age 30 at the earliest (preferably in a research setting)
2772:
Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, et al. (March 2020).
1307:
Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, et al. (October 2009).
1224:
There are a number of non-profit organisations providing information and support, including
4534:
2089:
2000:
1154:
825:
810:
533:
237:
47:
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1441:
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surveillance should then be performed at a 1-2 year interval for Lynch Syndrome patients.
8:
4930:
4852:
4734:
4002:
2657:
2495:"A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome"
1205:
1079:
Colorectal cancer with MSI-high pathology in a person who is younger than 60 years of age
910:
898:
but researchers are trying to use artificial intelligence to predict MSI from histology.
829:
798:
580:
517:
241:
139:
138:. The increased risk for these cancers is due to inherited genetic mutations that impair
3898:
2756:
2174:
Ou J, Rasmussen M, Westers H, Andersen SD, Jager PO, Kooi KA, et al. (April 2009).
2093:
2004:
4594:
4576:
4516:
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4341:
3790:
3765:
3702:
3677:
3653:
3628:
3604:
3560:
3455:
3430:
3401:
3376:
3303:
3248:
3223:
3222:
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. (June 2015).
3199:
3174:
3137:
3087:
2989:
2956:
2895:
2868:
2849:
2798:
2773:
2739:
2685:
2633:
2606:
2577:
2521:
2470:
2435:
2354:
2306:
2279:
2260:
2216:
2156:
2113:
2059:
1853:
1770:
1743:
1647:
1587:
1554:
1530:
1495:
1333:
1308:
1284:
1249:
1209:
1158:
949:
921:
806:
778:
513:
505:
277:
123:
107:
103:
16:
Autosomal dominant genetic condition associated with a high risk of cancer in the colon
4011:
4007:
3030:
3013:
4817:
4661:
4613:
4604:
4327:
4229:
4198:
4045:
3944:
3934:
3834:
3795:
3746:
3707:
3658:
3627:
Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, et al. (April 2005).
3609:
3552:
3517:
3460:
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3307:
3295:
3253:
3204:
3156:
3129:
3079:
3035:
2994:
2976:
2900:
2841:
2803:
2743:
2731:
2690:
2638:
2582:
2526:
2475:
2457:
2411:
2346:
2311:
2252:
2208:
2148:
2105:
2051:
2016:
1973:
1932:
1897:
1892:
1875:
1857:
1845:
1810:
1775:
1724:
1639:
1631:
1592:
1574:
1535:
1517:
1475:
1431:
1404:
1338:
1289:
1271:
1179:
794:
544:
272:
233:
63:
3564:
3141:
2853:
2358:
2264:
2220:
2160:
2063:
1950:
Le S, Ansari U, Mumtaz A, Malik K, Patel P, Doyle A, Khachemoune A (November 2017).
1651:
500:
4462:
4336:
4251:
4239:
3826:
3785:
3777:
3738:
3725:
Gologan A, Krasinskas A, Hunt J, Thull DL, Farkas L, Sepulveda AR (November 2005).
3697:
3689:
3648:
3640:
3599:
3591:
3544:
3509:
3450:
3442:
3396:
3388:
3285:
3243:
3235:
3194:
3186:
3121:
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3071:
3025:
2984:
2968:
2890:
2880:
2833:
2793:
2785:
2721:
2680:
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2628:
2618:
2572:
2564:
2516:
2508:
2465:
2447:
2403:
2338:
2301:
2291:
2244:
2198:
2190:
2140:
2117:
2097:
2043:
2008:
1963:
1924:
1887:
1837:
1802:
1765:
1755:
1714:
1665:
1623:
1582:
1566:
1525:
1507:
1396:
1361:
1328:
1320:
1279:
1261:
1171:
543:
The 4 main genes involved in Lynch syndrome normally encode for proteins that form
3377:"Recent progress in Lynch syndrome and other familial colorectal cancer syndromes"
4921:
4751:
4739:
4304:
4287:
4106:
4039:
3742:
3548:
3321:
2759:. From Medscape. By Juan Carlos Munoz and Louis R Lambiase. Updated: Oct 31, 2011
2407:
1689:
1400:
1073:
883:
315:
256:
245:
143:
1610:
Ring, Kari L.; Garcia, Christine; Thomas, Martha H.; Modesitt, Susan C. (2017).
1512:
309:
upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancer risk
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4916:
4838:
4618:
4581:
4511:
4409:
4349:
4292:
4221:
4211:
3513:
3446:
2972:
2837:
2789:
2726:
2709:
1841:
1627:
1570:
1463:
1194:
1183:
1134:
1110:
978:
967:
849:
841:
560:
303:
281:
115:
111:
4074:
4050:
3948:
3595:
3190:
3125:
3075:
2342:
2296:
1760:
777:
Up to 39% of families with mutations in a Lynch syndrome gene do not meet the
4966:
4910:
4826:
4562:
4244:
4141:
3644:
3274:"Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer"
2980:
2461:
1635:
1578:
1521:
1275:
1266:
932:
249:
168:
Lifetime risk and mean age at diagnosis for Lynch syndrome–associated cancers
127:
4137:
National Cancer Institute: Genetics of Colorectal Cancer information summary
3992:
3988:
3830:
2885:
2623:
2605:
Evrard C, Tachon G, Randrian V, Karayan-Tapon L, Tougeron D (October 2019).
2452:
2248:
2012:
1806:
566:
MSH2 protein dimerizes with MSH6 protein, which identifies mismatches via a
4524:
3838:
3799:
3750:
3711:
3662:
3613:
3556:
3464:
3410:
3299:
3257:
3208:
3160:
3133:
3083:
3039:
2998:
2904:
2845:
2807:
2735:
2694:
2676:
2642:
2586:
2530:
2479:
2415:
2350:
2315:
2256:
2212:
1977:
1936:
1849:
1814:
1779:
1728:
1719:
1702:
1643:
1611:
1596:
1539:
1479:
1408:
1342:
1324:
1293:
1098:
894:
The histopathological criteria are not sensitive enough to detect MSI from
264:
92:
55:
3781:
3521:
3290:
3273:
3239:
2152:
2109:
2055:
2020:
1901:
1612:"Current and future role of genetic screening in gynecologic malignancies"
4880:
4589:
4542:
4485:
4429:
4069:
1968:
1951:
1056:
information to help health care providers identify persons at high risk.
1027:
989:
858:
268:
135:
131:
2866:
2656:
Nouri Nojadeh, Jafar; Behrouz Sharif, Shahin; Sakhinia, Ebrahim (2018).
1928:
1492:
4800:
4777:
4675:
3392:
2047:
1175:
981:, starting at age 30 at the earliest (preferably in a research setting)
852:
from both a tumor tissue sample and a normal tissue sample followed by
537:
106:
genetic condition that is associated with a high risk of colon cancer,
39:
3971:
2194:
2144:
1869:
1867:
1208:
defect, and use the term "familial colorectal cancer type X" when the
1204:
Other sources reserve the term "Lynch syndrome" when there is a known
909:(HNPCC associated with other cancers of the gastrointestinal tract or
4571:
4494:
4312:
3856:
2568:
2550:
2512:
2494:
2101:
1126:
1045:
One or more of the HNPCC-related cancers diagnosed under age 50 years
895:
567:
529:
3931:
Daughter of Family G. : a memoir of cancer genes, love and fate
2033:
1552:
4782:
4761:
4634:
4080:
3693:
2655:
1864:
552:
260:
68:
2604:
520:, which causes an elevated rate of single nucleotide changes and
4028:
4025:
4022:
3675:
3347:"Work starts on a cancer vaccine for people with Lynch syndrome"
2548:
2233:
873:– MSI) cancers can be recognized by histopathological criteria:
641:
610:
524:, also known as MSI-H (the H is "high"). MSI is identifiable in
3983:
2492:
1106:
732:
525:
1990:
1741:
2771:
2433:
2392:
1827:
1386:
1114:
3486:
2954:
2079:
1034:
Amsterdam Criteria II (all bullet points must be fulfilled):
4631:
3899:"CDC: March 22nd is National Lynch Syndrome Awareness Day!"
3812:
2373:"Fact Sheet 33 | BOWEL CANCER AND INHERITED PREDISPOSITION"
1309:"Risk of pancreatic cancer in families with Lynch syndrome"
1306:
752:
711:
690:
669:
648:
617:
589:
576:
532:
laboratory. Most cases result in changes in the lengths of
480:
465:
444:
429:
3724:
2173:
793:
A diagnosis of Lynch syndrome is applied to people with a
259:
and common signs and symptoms include blood in the stool,
3322:"Lynchvax: Vaccine hope for cancer risk genetic disorder"
3224:"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency"
2328:
1461:
3763:
2823:
2130:
1609:
3626:
3499:
3172:
3011:
1873:
3012:
Vasen HF, Watson P, Mecklin JP, Lynch HT (June 1999).
2707:
1700:
1161:
but clinical trials are far from being conducted yet.
1016:
One or more colon cancers diagnosed under age 50 years
828:(IHC) is a method that can be used to detect abnormal
809:
and Bethesda Guidelines, or through tumor analysis by
1462:
Braun MM, Overbeek-Wager EA, Grumbo RJ (March 2016).
516:
fashion. The hallmark of Lynch syndrome is defective
3961:
3428:
3374:
1133:
There is an ongoing controversy over the benefit of
149:
Other HNPCC conditions include Lynch-like syndrome,
1949:
1701:Oki E, Oda S, Maehara Y, Sugimachi K (March 1999).
992:
or spinal cord), starting at age 25 at the earliest
3270:
3221:
1248:Carethers, John M; Stoffel, Elena M (2015-08-21).
844:), otherwise known as microsatellite instability (
3173:Boland CR, Koi M, Chang DK, Carethers JM (2007).
2658:"Microsatellite instability in colorectal cancer"
984:Annual physical and neurological exams to detect
4964:
1464:"Diagnosis and Management of Endometrial Cancer"
1247:
886:in any location showing any measurable level of
540:cytosine and adenine (sequence: CACACACACA...).
4973:DNA replication and repair-deficiency disorders
4116:GeneReviews/NCBI/NIH/UW entry on Lynch syndrome
3731:Archives of Pathology & Laboratory Medicine
3534:
3429:Biller LH, Syngal S, Yurgelun MB (April 2019).
1430:(2nd ed.). New York: McGraw-Hill Medical.
4993:Syndromes affecting the gastrointestinal tract
4171:
3375:Boland PM, Yurgelun MB, Boland CR (May 2018).
2075:
2073:
1914:
98:HNPCC includes (and was once synonymous with)
54:-H tumours, as may be seen in Lynch syndrome.
4720:
4157:
2826:American Journal of Obstetrics and Gynecology
2701:
2429:
2427:
2425:
2277:
1616:American Journal of Obstetrics and Gynecology
835:
412:Risk of gynecologic cancer in Lynch syndrome
3806:
3757:
3718:
3669:
3620:
3571:
2322:
2271:
2227:
2167:
1141:Anti-PD-1 antibody therapy can be effective.
151:polymerase proofreading-associated polyposis
3493:
3061:
2124:
2070:
4727:
4713:
4164:
4150:
3953:Paperback version retitled Before My Time.
3584:Surgical Oncology Clinics of North America
2422:
2204:11370/b74f7d2b-12fb-4bfc-a8c8-2d8950e81972
1830:International Journal of Clinical Oncology
1213:have a DNA-mismatch-repair gene mutation.
801:genes (MLH1, MSH2, MSH6, and PMS2) or the
73:
30:
4861:Hereditary nonpolyposis colorectal cancer
4420:Hereditary nonpolyposis colorectal cancer
3789:
3701:
3652:
3603:
3454:
3400:
3289:
3247:
3198:
3029:
2988:
2894:
2884:
2797:
2725:
2684:
2632:
2622:
2576:
2520:
2469:
2451:
2305:
2295:
2202:
1967:
1891:
1792:
1769:
1759:
1718:
1586:
1529:
1511:
1332:
1283:
1265:
1068:Colorectal cancer diagnosed before age 50
877:right-sided poorly differentiated cancers
598:Frequency of mutations in HNPCC families
255:Two-thirds of colon cancers occur in the
85:Hereditary nonpolyposis colorectal cancer
25:Hereditary nonpolyposis colorectal cancer
3770:Journal of the National Cancer Institute
3528:
3111:
1030:, small bowel, ureter and renal pelvis.
499:
4645:Intraductal papillary mucinous neoplasm
2757:Hereditary Colorectal Cancer Background
1421:
901:In addition, HNPCC can be divided into
820:
153:and familial colorectal cancer type X.
4965:
3577:
2600:
2598:
2596:
2284:Hereditary Cancer in Clinical Practice
4708:
4145:
3928:
3424:
3422:
3420:
3370:
3368:
3366:
3107:
3105:
3103:
3101:
3057:
3055:
3053:
3051:
3049:
2950:
2948:
2946:
2920:
2918:
2916:
2914:
2819:
2817:
2767:
2765:
2544:
2542:
2540:
2388:
2386:
1356:
1354:
1352:
1243:
1241:
996:
156:
3344:
2649:
986:cancer in the central nervous system
570:, a protein for scanning for errors.
91:) is a hereditary predisposition to
4694:Desmoplastic small round cell tumor
3933:. Toronto: Alfred A. Knopf Canada.
3431:"Recent advances in Lynch syndrome"
3381:CA: A Cancer Journal for Clinicians
3228:The New England Journal of Medicine
2593:
1199:Creighton University Medical Center
1042:Two successive affected generations
1013:Two successive affected generations
557:single-stranded-DNA binding-protein
13:
4395:Polymerase proofreading-associated
3917:
3682:American Journal of Human Genetics
3417:
3363:
3098:
3046:
2943:
2911:
2814:
2762:
2537:
2383:
1349:
1238:
512:Lynch syndrome is inherited in an
14:
5004:
4257:Hereditary diffuse gastric cancer
3957:
3878:"Bowel Cancer UK: Lynch Syndrome"
2278:Suchy J, Lubinski J (June 2008).
1254:World Journal of Gastroenterology
864:
161:
4948:Severe combined immunodeficiency
4553:Nodular regenerative hyperplasia
3351:Cancer Research UK - Cancer News
1424:"Chapter 33: Endometrial Cancer"
1389:Diseases of the Colon and Rectum
4871:Mismatch repair cancer syndrome
3891:
3870:
3849:
3471:
3338:
3314:
3278:New England Journal of Medicine
3264:
3215:
3166:
3148:
3114:Digestive Diseases and Sciences
3064:Digestive Diseases and Sciences
3005:
2860:
2750:
2486:
2365:
2183:Genes, Chromosomes & Cancer
2027:
1984:
1943:
1908:
1821:
1786:
1735:
1694:
1676:
1658:
1164:
4744:DNA repair-deficiency disorder
4655:Solid pseudopapillary neoplasm
4458:Gastrointestinal stromal tumor
4415:Familial adenomatous polyposis
3537:Advances in Anatomic Pathology
1603:
1546:
1486:
1455:
1415:
1380:
1300:
1189:
1049:Familial adenomatous polyposis
1020:Familial adenomatous polyposis
236:, ureter/renal pelvis cancer,
182:Mean age at diagnosis (years)
44:tumor-infiltrating lymphocytes
1:
4463:Krukenberg tumor (metastatic)
3502:Archives of Internal Medicine
3031:10.1016/S0016-5085(99)70510-X
1231:
869:Three major groups of MSI-H (
50:), a finding associated with
4822:DeSanctis–Cacchione syndrome
4768:Aicardi–Goutières syndrome 4
4684:Primary peritoneal carcinoma
4358:traditional serrated adenoma
4111:National Institute of Health
3819:Journal of Clinical Oncology
3743:10.5858/2005-129-1390-POTRBG
3549:10.1097/PAP.0b013e3181bb6bdc
2556:Health Technology Assessment
2500:Health Technology Assessment
2408:10.1053/j.gastro.2014.04.001
1893:10.1016/0092-8674(93)90546-3
1795:Journal of Clinical Oncology
1401:10.1097/DCR.0000000000000926
1226:Lynch Syndrome International
1120:
977:Annual urinalysis to detect
966:Upper endoscopies to detect
916:
905:(familial colon cancer) and
880:right-sided mucinous cancers
788:
7:
4624:Pancreatic ductal carcinoma
1513:10.3390/diagnostics10100786
1197:, Professor of Medicine at
1148:
1060:Revised Bethesda Guidelines
807:Amsterdam Clinical Criteria
495:
312:urinary tract cancers risk
10:
5009:
4894:Nijmegen breakage syndrome
4810:Nucleotide excision repair
4640:Serous microcystic adenoma
4235:Signet ring cell carcinoma
4173:Digestive system neoplasia
3578:Lindor NM (October 2009).
3514:10.1001/archinte.117.2.206
3447:10.1007/s10689-018-00117-1
2973:10.1136/gutjnl-2012-304356
2838:10.1016/j.ajog.2017.04.011
2790:10.1136/gutjnl-2019-319915
2727:10.1016/j.ejca.2022.07.020
2714:European Journal of Cancer
1956:Dermatology Online Journal
1842:10.1007/s10147-019-01494-y
1628:10.1016/j.ajog.2017.04.011
1571:10.1136/gutjnl-2017-314057
1219:
1092:
940:Endometrial/ovarian cancer
888:intraepithelial lymphocyte
871:microsatellite instability
836:Microsatellite instability
815:microsatellite instability
595:Genes implicated in HNPCC
522:microsatellite instability
4927:Rothmund–Thomson syndrome
4902:
4879:
4847:
4808:
4799:
4750:
4674:
4603:
4561:
4548:Focal nodular hyperplasia
4484:
4475:
4450:
4428:
4326:
4303:
4278:
4269:
4220:
4197:
4188:
4179:
4060:
3965:
3596:10.1016/j.soc.2009.07.003
3191:10.1007/s10689-007-9145-9
3126:10.1007/s10620-016-4346-4
3076:10.1007/s10620-015-3964-6
2343:10.1007/s10689-009-9298-9
2297:10.1186/1897-4287-6-2-103
1761:10.1186/s12885-018-4489-0
1468:American Family Physician
504:HNPCC is inherited in an
62:
38:
29:
24:
4650:Mucinous cystic neoplasm
4500:Hepatocellular carcinoma
4354:sessile serrated adenoma
3922:
3645:10.1001/jama.293.16.1979
3345:Gunn, Tim (2024-09-09).
1267:10.3748/wjg.v21.i31.9253
575:with other mutations in
423:Endometrial cancer risk
300:endometrial cancer risk
4759:Separation/initiation:
4689:Peritoneal mesothelioma
4438:Squamous cell carcinoma
4207:Squamous cell carcinoma
3831:10.1200/JCO.2004.11.084
2926:"Medical Options | CDC"
2886:10.3390/cancers12071874
2624:10.3390/cancers11101567
2453:10.3390/cancers13030391
2249:10.1136/gut.2008.156695
2013:10.1126/science.8128251
1807:10.1200/JCO.2003.04.060
1670:Genetics Home Reference
1051:(FAP) has been excluded
1022:(FAP) has been excluded
946:transvaginal ultrasound
297:colorectal cancer risk
4789:Dyskeratosis congenita
4530:Hepatocellular adenoma
4318:Pseudomyxoma peritonei
2677:10.17179/EXCLI2017-948
1720:10.1038/sj.onc.1202583
1325:10.1001/jama.2009.1529
696:relatively infrequent
509:
110:(second most common),
4988:Syndromes with tumors
4889:Ataxia–telangiectasia
4832:Xeroderma pigmentosum
3291:10.1056/NEJMoa2017699
3240:10.1056/NEJMoa1500596
1103:salpingo-oophorectomy
795:germline DNA mutation
503:
4943:Li–Fraumeni syndrome
4535:Cavernous hemangioma
4386:Familial adenomatous
4373:Polyposis syndromes:
1969:10.5070/D32311037239
1155:University of Oxford
826:Immunohistochemistry
821:Immunohistochemistry
811:immunohistochemistry
534:dinucleotide repeats
420:Ovarian cancer risk
244:. Increased risk of
240:, brain cancer, and
238:biliary tract cancer
4931:RAPADILINO syndrome
4866:Muir–Torre syndrome
4853:DNA mismatch repair
3929:McKay, Ami (2019).
3857:"Lynch Syndrome UK"
3782:10.1093/jnci/djh034
2094:1994Natur.371...75N
2005:1994Sci...263.1625P
1929:10.1200/EDBK_208341
1428:Williams Gynecology
1422:Hoffman BL (2012).
1368:. February 22, 2019
1206:DNA mismatch repair
911:reproductive system
581:DNA mismatch repair
568:sliding clamp model
518:DNA mismatch repair
486:6% (combined risk)
413:
242:sebaceous neoplasms
140:DNA mismatch repair
124:hepatobiliary tract
4983:Hereditary cancers
4595:Gallbladder cancer
4577:Cholangiocarcinoma
4517:Liver angiosarcoma
4451:Upper and/or lower
4400:Serrated polyposis
4105:2007-08-15 at the
4061:External resources
3393:10.3322/caac.21448
2048:10.1038/ng1197-271
1688:2006-06-19 at the
1210:Amsterdam criteria
1159:Cancer Research UK
1157:with a grant from
997:Amsterdam criteria
950:endometrial biopsy
922:Genetic counseling
779:Amsterdam criteria
660:Papadopoulos 1994
654:approximately 30%
629:approximately 60%
604:First publication
514:autosomal dominant
510:
506:autosomal dominant
411:
278:endometrial cancer
271:. The mean age of
179:Lifetime risk (%)
157:Signs and symptoms
142:. It is a type of
108:endometrial cancer
104:autosomal dominant
4978:Colorectal cancer
4960:
4959:
4956:
4955:
4818:Cockayne syndrome
4736:Metabolic disease
4702:
4701:
4670:
4669:
4662:Pancreatoblastoma
4614:exocrine pancreas
4471:
4470:
4446:
4445:
4265:
4264:
4230:Gastric carcinoma
4095:
4094:
3940:978-0-345-80946-9
3489:on July 22, 2011.
3284:(23): 2207–2218.
2195:10.1002/gcc.20644
2145:10.1038/ng0598-17
1260:(31): 9253–9261.
1180:African Americans
907:Lynch syndrome II
767:
766:
528:specimens in the
493:
492:
409:
408:
321:brain tumor risk
273:colorectal cancer
267:, and unintended
234:pancreatic cancer
230:
229:
82:
81:
48:colorectal cancer
19:Medical condition
5000:
4806:
4805:
4729:
4722:
4715:
4706:
4705:
4482:
4481:
4381:MUTYH-associated
4366:Cronkhite–Canada
4337:Colorectal polyp
4276:
4275:
4252:Linitis plastica
4240:Gastric lymphoma
4195:
4194:
4186:
4185:
4166:
4159:
4152:
4143:
4142:
3963:
3962:
3952:
3911:
3910:
3908:
3906:
3895:
3889:
3888:
3886:
3884:
3874:
3868:
3867:
3865:
3863:
3853:
3847:
3846:
3841:. Archived from
3810:
3804:
3803:
3793:
3761:
3755:
3754:
3722:
3716:
3715:
3705:
3673:
3667:
3666:
3656:
3624:
3618:
3617:
3607:
3575:
3569:
3568:
3532:
3526:
3525:
3497:
3491:
3490:
3485:. Archived from
3483:www.oncolink.org
3475:
3469:
3468:
3458:
3426:
3415:
3414:
3404:
3372:
3361:
3360:
3358:
3357:
3342:
3336:
3335:
3333:
3332:
3318:
3312:
3311:
3293:
3268:
3262:
3261:
3251:
3219:
3213:
3212:
3202:
3170:
3164:
3152:
3146:
3145:
3109:
3096:
3095:
3059:
3044:
3043:
3033:
3018:Gastroenterology
3009:
3003:
3002:
2992:
2952:
2941:
2940:
2938:
2937:
2922:
2909:
2908:
2898:
2888:
2864:
2858:
2857:
2821:
2812:
2811:
2801:
2769:
2760:
2754:
2748:
2747:
2729:
2705:
2699:
2698:
2688:
2662:
2653:
2647:
2646:
2636:
2626:
2602:
2591:
2590:
2580:
2569:10.3310/hta21510
2546:
2535:
2534:
2524:
2513:10.3310/hta18580
2490:
2484:
2483:
2473:
2455:
2431:
2420:
2419:
2396:Gastroenterology
2390:
2381:
2380:
2375:. Archived from
2369:
2363:
2362:
2326:
2320:
2319:
2309:
2299:
2275:
2269:
2268:
2231:
2225:
2224:
2206:
2180:
2171:
2165:
2164:
2128:
2122:
2121:
2102:10.1038/371075a0
2077:
2068:
2067:
2031:
2025:
2024:
1999:(5153): 1625–9.
1988:
1982:
1981:
1971:
1947:
1941:
1940:
1912:
1906:
1905:
1895:
1871:
1862:
1861:
1825:
1819:
1818:
1790:
1784:
1783:
1773:
1763:
1739:
1733:
1732:
1722:
1698:
1692:
1680:
1674:
1673:
1666:"Lynch Syndrome"
1662:
1656:
1655:
1607:
1601:
1600:
1590:
1565:(7): 1306–1316.
1550:
1544:
1543:
1533:
1515:
1490:
1484:
1483:
1459:
1453:
1452:
1450:
1449:
1440:. Archived from
1419:
1413:
1412:
1395:(10): 999–1017.
1384:
1378:
1377:
1375:
1373:
1362:"Lynch Syndrome"
1358:
1347:
1346:
1336:
1304:
1298:
1297:
1287:
1269:
1245:
1172:French Canadians
1105:(removal of the
1074:keratoacanthomas
948:with or without
903:Lynch syndrome I
723:Nicolaides 1994
702:Nicolaides 1994
586:
585:
579:involved in the
414:
410:
291:
290:
173:
172:
78:
77:
34:
22:
21:
5008:
5007:
5003:
5002:
5001:
4999:
4998:
4997:
4963:
4962:
4961:
4952:
4922:Werner syndrome
4898:
4875:
4843:
4795:
4752:DNA replication
4746:
4740:DNA replication
4733:
4703:
4698:
4666:
4599:
4557:
4467:
4442:
4424:
4322:
4299:
4288:Duodenal cancer
4280:Small intestine
4261:
4216:
4175:
4170:
4107:Wayback Machine
4096:
4091:
4090:
4056:
4055:
3974:
3960:
3941:
3925:
3920:
3918:Further reading
3915:
3914:
3904:
3902:
3897:
3896:
3892:
3882:
3880:
3876:
3875:
3871:
3861:
3859:
3855:
3854:
3850:
3825:(24): 4934–43.
3811:
3807:
3762:
3758:
3723:
3719:
3674:
3670:
3639:(16): 1979–85.
3625:
3621:
3576:
3572:
3533:
3529:
3498:
3494:
3477:
3476:
3472:
3435:Familial Cancer
3427:
3418:
3373:
3364:
3355:
3353:
3343:
3339:
3330:
3328:
3320:
3319:
3315:
3269:
3265:
3234:(26): 2509–20.
3220:
3216:
3179:Familial Cancer
3171:
3167:
3153:
3149:
3110:
3099:
3060:
3047:
3010:
3006:
2953:
2944:
2935:
2933:
2924:
2923:
2912:
2865:
2861:
2822:
2815:
2770:
2763:
2755:
2751:
2706:
2702:
2660:
2654:
2650:
2603:
2594:
2547:
2538:
2491:
2487:
2432:
2423:
2391:
2384:
2371:
2370:
2366:
2331:Familial Cancer
2327:
2323:
2280:"MSH6 syndrome"
2276:
2272:
2243:(11): 1539–44.
2232:
2228:
2178:
2172:
2168:
2133:Nature Genetics
2129:
2125:
2088:(6492): 75–80.
2078:
2071:
2036:Nature Genetics
2032:
2028:
1989:
1985:
1948:
1944:
1923:(38): 101–109.
1913:
1909:
1872:
1865:
1836:(9): 999–1011.
1826:
1822:
1791:
1787:
1740:
1736:
1699:
1695:
1690:Wayback Machine
1681:
1677:
1664:
1663:
1659:
1608:
1604:
1551:
1547:
1491:
1487:
1460:
1456:
1447:
1445:
1438:
1420:
1416:
1385:
1381:
1371:
1369:
1360:
1359:
1350:
1305:
1301:
1246:
1239:
1234:
1222:
1192:
1167:
1151:
1123:
1111:fallopian tubes
1095:
999:
919:
884:adenocarcinomas
867:
842:microsatellites
838:
830:mismatch repair
823:
791:
561:DNA polymerases
498:
316:prostate cancer
246:prostate cancer
176:Type of cancer
164:
159:
144:cancer syndrome
120:small intestine
72:
20:
17:
12:
11:
5:
5006:
4996:
4995:
4990:
4985:
4980:
4975:
4958:
4957:
4954:
4953:
4951:
4950:
4945:
4940:
4938:Fanconi anemia
4935:
4934:
4933:
4924:
4919:
4917:Bloom syndrome
4906:
4904:
4900:
4899:
4897:
4896:
4891:
4885:
4883:
4877:
4876:
4874:
4873:
4868:
4863:
4857:
4855:
4845:
4844:
4842:
4841:
4839:IBIDS syndrome
4836:
4835:
4834:
4824:
4814:
4812:
4803:
4797:
4796:
4794:
4793:
4792:
4791:
4773:
4772:
4771:
4770:
4756:
4754:
4748:
4747:
4732:
4731:
4724:
4717:
4709:
4700:
4699:
4697:
4696:
4691:
4686:
4680:
4678:
4672:
4671:
4668:
4667:
4665:
4664:
4658:
4657:
4652:
4647:
4642:
4627:
4626:
4621:
4619:Adenocarcinoma
4609:
4607:
4601:
4600:
4598:
4597:
4585:
4584:
4582:Klatskin tumor
4579:
4567:
4565:
4559:
4558:
4556:
4555:
4550:
4538:
4537:
4532:
4520:
4519:
4514:
4512:Hepatoblastoma
4509:
4508:
4507:
4490:
4488:
4479:
4473:
4472:
4469:
4468:
4466:
4465:
4460:
4454:
4452:
4448:
4447:
4444:
4443:
4441:
4440:
4434:
4432:
4426:
4425:
4423:
4422:
4417:
4412:
4410:Adenocarcinoma
4403:
4402:
4397:
4392:
4383:
4378:
4369:
4368:
4332:
4330:
4324:
4323:
4321:
4320:
4315:
4309:
4307:
4301:
4300:
4298:
4297:
4296:
4295:
4293:Adenocarcinoma
4284:
4282:
4273:
4267:
4266:
4263:
4262:
4260:
4259:
4254:
4249:
4248:
4247:
4237:
4232:
4226:
4224:
4218:
4217:
4215:
4214:
4212:Adenocarcinoma
4209:
4203:
4201:
4192:
4183:
4177:
4176:
4169:
4168:
4161:
4154:
4146:
4140:
4139:
4134:
4118:
4113:
4093:
4092:
4089:
4088:
4077:
4075:Lynch Syndrome
4065:
4064:
4062:
4058:
4057:
4054:
4053:
4042:
4031:
4014:
3995:
3975:
3970:
3969:
3967:
3966:Classification
3959:
3958:External links
3956:
3955:
3954:
3939:
3924:
3921:
3919:
3916:
3913:
3912:
3890:
3869:
3848:
3845:on 2013-04-15.
3805:
3756:
3737:(11): 1390–7.
3717:
3694:10.1086/316942
3688:(1): 118–127.
3668:
3619:
3570:
3527:
3492:
3470:
3441:(2): 211–219.
3416:
3387:(3): 217–231.
3362:
3337:
3313:
3263:
3214:
3165:
3147:
3120:(2): 299–304.
3097:
3045:
3004:
2967:(6): 812–823.
2942:
2910:
2859:
2832:(5): 512–521.
2813:
2784:(3): 411–444.
2761:
2749:
2700:
2648:
2592:
2536:
2485:
2421:
2382:
2379:on 2019-02-28.
2364:
2321:
2270:
2226:
2166:
2123:
2069:
2026:
1983:
1942:
1907:
1886:(5): 1027–38.
1863:
1820:
1785:
1734:
1713:(12): 2143–7.
1693:
1675:
1657:
1622:(5): 512–521.
1602:
1545:
1485:
1454:
1437:978-0071716727
1436:
1414:
1379:
1348:
1319:(16): 1790–5.
1299:
1236:
1235:
1233:
1230:
1221:
1218:
1195:Henry T. Lynch
1191:
1188:
1184:Ashkenazi Jews
1166:
1163:
1150:
1147:
1143:
1142:
1135:5-fluorouracil
1122:
1119:
1094:
1091:
1087:
1086:
1083:
1080:
1077:
1069:
1053:
1052:
1046:
1043:
1040:
1024:
1023:
1017:
1014:
1011:
998:
995:
994:
993:
982:
979:bladder cancer
975:
918:
915:
892:
891:
881:
878:
866:
865:Classification
863:
850:DNA extraction
837:
834:
822:
819:
797:in one of the
790:
787:
774:detecting it.
765:
764:
762:
759:
756:
749:
745:
744:
742:
739:
736:
729:
725:
724:
721:
718:
715:
708:
704:
703:
700:
697:
694:
687:
683:
682:
679:
676:
673:
666:
662:
661:
658:
655:
652:
645:
637:
636:
633:
630:
627:
614:
606:
605:
602:
599:
596:
593:
572:
571:
564:
497:
494:
491:
490:
487:
484:
476:
475:
472:
469:
461:
460:
457:
454:
440:
439:
436:
433:
425:
424:
421:
418:
407:
406:
403:
400:
397:
394:
391:
388:
385:
379:
378:
375:
372:
369:
366:
363:
360:
357:
351:
350:
347:
344:
341:
338:
335:
332:
329:
323:
322:
319:
313:
310:
307:
304:ovarian cancer
301:
298:
295:
282:gastric cancer
257:proximal colon
228:
227:
224:
221:
217:
216:
213:
210:
206:
205:
202:
199:
195:
194:
191:
188:
184:
183:
180:
177:
163:
162:Risk of cancer
160:
158:
155:
100:Lynch syndrome
80:
79:
66:
60:
59:
36:
35:
27:
26:
18:
15:
9:
6:
4:
3:
2:
5005:
4994:
4991:
4989:
4986:
4984:
4981:
4979:
4976:
4974:
4971:
4970:
4968:
4949:
4946:
4944:
4941:
4939:
4936:
4932:
4928:
4925:
4923:
4920:
4918:
4915:
4914:
4913:
4912:
4911:RecQ helicase
4908:
4907:
4905:
4901:
4895:
4892:
4890:
4887:
4886:
4884:
4882:
4878:
4872:
4869:
4867:
4864:
4862:
4859:
4858:
4856:
4854:
4850:
4846:
4840:
4837:
4833:
4830:
4829:
4828:
4827:Thymine dimer
4825:
4823:
4819:
4816:
4815:
4813:
4811:
4807:
4804:
4802:
4798:
4790:
4787:
4786:
4785:
4784:
4779:
4775:
4774:
4769:
4766:
4765:
4764:
4763:
4758:
4757:
4755:
4753:
4749:
4745:
4741:
4737:
4730:
4725:
4723:
4718:
4716:
4711:
4710:
4707:
4695:
4692:
4690:
4687:
4685:
4682:
4681:
4679:
4677:
4673:
4663:
4660:
4659:
4656:
4653:
4651:
4648:
4646:
4643:
4641:
4637:
4636:
4633:
4629:
4628:
4625:
4622:
4620:
4617:
4615:
4611:
4610:
4608:
4606:
4602:
4596:
4593:
4591:
4587:
4586:
4583:
4580:
4578:
4575:
4573:
4569:
4568:
4566:
4564:
4563:Biliary tract
4560:
4554:
4551:
4549:
4546:
4544:
4540:
4539:
4536:
4533:
4531:
4528:
4526:
4522:
4521:
4518:
4515:
4513:
4510:
4506:
4505:Fibrolamellar
4503:
4502:
4501:
4498:
4496:
4492:
4491:
4489:
4487:
4483:
4480:
4478:
4474:
4464:
4461:
4459:
4456:
4455:
4453:
4449:
4439:
4436:
4435:
4433:
4431:
4427:
4421:
4418:
4416:
4413:
4411:
4408:
4405:
4404:
4401:
4398:
4396:
4393:
4391:
4387:
4384:
4382:
4379:
4377:
4374:
4371:
4370:
4367:
4363:
4362:Peutz–Jeghers
4359:
4355:
4351:
4347:
4343:
4340:
4338:
4334:
4333:
4331:
4329:
4325:
4319:
4316:
4314:
4311:
4310:
4308:
4306:
4302:
4294:
4291:
4290:
4289:
4286:
4285:
4283:
4281:
4277:
4274:
4272:
4268:
4258:
4255:
4253:
4250:
4246:
4245:MALT lymphoma
4243:
4242:
4241:
4238:
4236:
4233:
4231:
4228:
4227:
4225:
4223:
4219:
4213:
4210:
4208:
4205:
4204:
4202:
4200:
4196:
4193:
4191:
4187:
4184:
4182:
4178:
4174:
4167:
4162:
4160:
4155:
4153:
4148:
4147:
4144:
4138:
4135:
4132:
4128:
4124:
4123:
4119:
4117:
4114:
4112:
4108:
4104:
4101:
4100:FAQs on HNPCC
4098:
4097:
4087:
4083:
4082:
4078:
4076:
4072:
4071:
4067:
4066:
4063:
4059:
4052:
4048:
4047:
4043:
4041:
4037:
4036:
4032:
4030:
4027:
4024:
4020:
4019:
4015:
4013:
4009:
4005:
4004:
4000:
3996:
3994:
3990:
3986:
3985:
3981:
3977:
3976:
3973:
3968:
3964:
3950:
3946:
3942:
3936:
3932:
3927:
3926:
3900:
3894:
3879:
3873:
3858:
3852:
3844:
3840:
3836:
3832:
3828:
3824:
3820:
3816:
3809:
3801:
3797:
3792:
3787:
3783:
3779:
3775:
3771:
3767:
3760:
3752:
3748:
3744:
3740:
3736:
3732:
3728:
3721:
3713:
3709:
3704:
3699:
3695:
3691:
3687:
3683:
3679:
3672:
3664:
3660:
3655:
3650:
3646:
3642:
3638:
3634:
3630:
3623:
3615:
3611:
3606:
3601:
3597:
3593:
3590:(4): 637–45.
3589:
3585:
3581:
3574:
3566:
3562:
3558:
3554:
3550:
3546:
3543:(6): 405–17.
3542:
3538:
3531:
3523:
3519:
3515:
3511:
3508:(2): 206–12.
3507:
3503:
3496:
3488:
3484:
3480:
3474:
3466:
3462:
3457:
3452:
3448:
3444:
3440:
3436:
3432:
3425:
3423:
3421:
3412:
3408:
3403:
3398:
3394:
3390:
3386:
3382:
3378:
3371:
3369:
3367:
3352:
3348:
3341:
3327:
3323:
3317:
3309:
3305:
3301:
3297:
3292:
3287:
3283:
3279:
3275:
3267:
3259:
3255:
3250:
3245:
3241:
3237:
3233:
3229:
3225:
3218:
3210:
3206:
3201:
3196:
3192:
3188:
3184:
3180:
3176:
3169:
3162:
3158:
3151:
3143:
3139:
3135:
3131:
3127:
3123:
3119:
3115:
3108:
3106:
3104:
3102:
3093:
3089:
3085:
3081:
3077:
3073:
3070:(4): 969–76.
3069:
3065:
3058:
3056:
3054:
3052:
3050:
3041:
3037:
3032:
3027:
3024:(6): 1453–6.
3023:
3019:
3015:
3008:
3000:
2996:
2991:
2986:
2982:
2978:
2974:
2970:
2966:
2962:
2958:
2951:
2949:
2947:
2931:
2927:
2921:
2919:
2917:
2915:
2906:
2902:
2897:
2892:
2887:
2882:
2878:
2874:
2870:
2863:
2855:
2851:
2847:
2843:
2839:
2835:
2831:
2827:
2820:
2818:
2809:
2805:
2800:
2795:
2791:
2787:
2783:
2779:
2775:
2768:
2766:
2758:
2753:
2745:
2741:
2737:
2733:
2728:
2723:
2719:
2715:
2711:
2704:
2696:
2692:
2687:
2682:
2678:
2674:
2670:
2666:
2665:EXCLI Journal
2659:
2652:
2644:
2640:
2635:
2630:
2625:
2620:
2616:
2612:
2608:
2601:
2599:
2597:
2588:
2584:
2579:
2574:
2570:
2566:
2563:(51): 1–238.
2562:
2558:
2557:
2552:
2545:
2543:
2541:
2532:
2528:
2523:
2518:
2514:
2510:
2507:(58): 1–406.
2506:
2502:
2501:
2496:
2489:
2481:
2477:
2472:
2467:
2463:
2459:
2454:
2449:
2445:
2441:
2437:
2430:
2428:
2426:
2417:
2413:
2409:
2405:
2402:(2): 502–26.
2401:
2397:
2389:
2387:
2378:
2374:
2368:
2360:
2356:
2352:
2348:
2344:
2340:
2337:(2): 141–50.
2336:
2332:
2325:
2317:
2313:
2308:
2303:
2298:
2293:
2289:
2285:
2281:
2274:
2266:
2262:
2258:
2254:
2250:
2246:
2242:
2238:
2230:
2222:
2218:
2214:
2210:
2205:
2200:
2196:
2192:
2189:(4): 340–50.
2188:
2184:
2177:
2170:
2162:
2158:
2154:
2150:
2146:
2142:
2138:
2134:
2127:
2119:
2115:
2111:
2107:
2103:
2099:
2095:
2091:
2087:
2083:
2076:
2074:
2065:
2061:
2057:
2053:
2049:
2045:
2041:
2037:
2030:
2022:
2018:
2014:
2010:
2006:
2002:
1998:
1994:
1987:
1979:
1975:
1970:
1965:
1961:
1957:
1953:
1946:
1938:
1934:
1930:
1926:
1922:
1918:
1911:
1903:
1899:
1894:
1889:
1885:
1881:
1877:
1870:
1868:
1859:
1855:
1851:
1847:
1843:
1839:
1835:
1831:
1824:
1816:
1812:
1808:
1804:
1801:(6): 1174–9.
1800:
1796:
1789:
1781:
1777:
1772:
1767:
1762:
1757:
1753:
1749:
1745:
1738:
1730:
1726:
1721:
1716:
1712:
1708:
1704:
1697:
1691:
1687:
1684:
1679:
1671:
1667:
1661:
1653:
1649:
1645:
1641:
1637:
1633:
1629:
1625:
1621:
1617:
1613:
1606:
1598:
1594:
1589:
1584:
1580:
1576:
1572:
1568:
1564:
1560:
1556:
1549:
1541:
1537:
1532:
1527:
1523:
1519:
1514:
1509:
1505:
1501:
1497:
1489:
1481:
1477:
1474:(6): 468–74.
1473:
1469:
1465:
1458:
1444:on 2014-01-04
1443:
1439:
1433:
1429:
1425:
1418:
1410:
1406:
1402:
1398:
1394:
1390:
1383:
1367:
1363:
1357:
1355:
1353:
1344:
1340:
1335:
1330:
1326:
1322:
1318:
1314:
1310:
1303:
1295:
1291:
1286:
1281:
1277:
1273:
1268:
1263:
1259:
1255:
1251:
1244:
1242:
1237:
1229:
1227:
1217:
1214:
1211:
1207:
1202:
1200:
1196:
1187:
1185:
1181:
1177:
1173:
1162:
1160:
1156:
1146:
1140:
1139:
1138:
1136:
1131:
1128:
1118:
1116:
1112:
1108:
1104:
1100:
1097:Prophylactic
1090:
1084:
1081:
1078:
1075:
1070:
1067:
1066:
1065:
1062:
1061:
1057:
1050:
1047:
1044:
1041:
1038:
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957:Other cancers
954:
951:
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937:
934:
933:Colonoscopies
930:
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56:H&E stain
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28:
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4909:
4860:
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4776:Termination/
4760:
4630:
4612:
4588:
4570:
4541:
4523:
4493:
4419:
4406:
4372:
4346:hyperplastic
4335:
4328:Colon/rectum
4120:
4079:
4068:
4044:
4033:
4016:
3997:
3978:
3930:
3903:. Retrieved
3901:. 2018-03-20
3893:
3881:. Retrieved
3872:
3860:. Retrieved
3851:
3843:the original
3822:
3818:
3808:
3776:(4): 261–8.
3773:
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3487:the original
3482:
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3350:
3340:
3329:. Retrieved
3325:
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3281:
3277:
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3231:
3227:
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3185:(1): 41–52.
3182:
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3021:
3017:
3007:
2964:
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2932:. 2020-04-01
2929:
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2829:
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2614:
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2290:(2): 103–4.
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2042:(3): 271–2.
2039:
2035:
2029:
1996:
1992:
1986:
1959:
1955:
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1920:
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1883:
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1467:
1457:
1446:. Retrieved
1442:the original
1427:
1417:
1392:
1388:
1382:
1372:November 18,
1370:. Retrieved
1365:
1316:
1312:
1302:
1257:
1253:
1223:
1215:
1203:
1193:
1168:
1165:Epidemiology
1152:
1144:
1132:
1124:
1099:hysterectomy
1096:
1088:
1063:
1059:
1058:
1054:
1033:
1032:
1025:
1004:
1003:
1000:
960:
956:
955:
943:
939:
938:
931:
928:Colon cancer
927:
926:
920:
906:
902:
900:
893:
868:
839:
824:
792:
783:
776:
770:
769:People with
768:
751:
738:case report
731:
717:case report
710:
689:
681:Miyaki 1997
668:
647:
635:Fishel 1993
622:
616:
573:
553:DNA helicase
542:
511:
479:
464:
449:
443:
428:
382:
354:
326:
287:
265:constipation
254:
231:
198:Endometrial
167:
166:
165:
148:
99:
97:
93:colon cancer
88:
84:
83:
4881:MRN complex
4590:gallbladder
4543:hyperplasia
4070:GeneReviews
3326:www.bbc.com
2930:www.cdc.gov
2879:(7): 1874.
2720:: 136–157.
2671:: 159–168.
2139:(1): 17–8.
1506:(10): 786.
1500:Diagnostics
1190:Terminology
1028:endometrium
972:small bowel
859:immunoscore
559:(RPA), and
538:nucleobases
269:weight loss
187:Colorectal
4967:Categories
4801:DNA repair
4778:telomerase
4676:Peritoneum
4046:DiseasesDB
3949:1089450897
3479:"Oncolink"
3356:2024-09-18
3331:2024-09-18
2936:2020-12-07
2446:(3): 391.
1754:(1): 576.
1748:BMC Cancer
1448:2014-06-23
1232:References
1176:Icelanders
813:(IHC), or
40:Micrograph
4635:neoplasms
4572:bile duct
4495:malignant
4477:Accessory
4407:Neoplasm:
4390:Gardner's
4313:Carcinoid
4199:Esophagus
4133:GeneTests
4109:from the
3308:227259533
2981:0017-5749
2744:252289107
2462:2072-6694
1858:195795805
1636:1097-6868
1579:1468-3288
1522:2075-4418
1276:1007-9327
1127:colectomy
1121:Treatment
917:Screening
896:histology
789:Diagnosis
758:disputed
720:2q31-q33
640:HNPCC2 (
609:HNPCC1 (
583:pathway:
530:pathology
64:Specialty
4762:RNASEH2A
4605:Pancreas
4376:Juvenile
4350:juvenile
4305:Appendix
4181:GI tract
4103:Archived
4081:Orphanet
3905:31 March
3883:31 March
3862:31 March
3839:15611508
3800:14970275
3751:16253017
3712:11112663
3663:15855431
3614:19793571
3565:25600795
3557:19851131
3465:30627969
3411:29485237
3300:33264544
3258:26028255
3209:17636426
3161:31378807
3142:32833106
3134:27990589
3084:26602911
3040:10348829
2999:23408351
2905:32664613
2854:29024566
2846:28411145
2808:31780574
2736:36115290
2695:29743854
2643:31618962
2587:28895526
2531:25244061
2480:33494280
2416:25043945
2359:25479413
2351:19851887
2316:19804606
2265:10608978
2257:18625694
2221:15526044
2213:19156873
2161:46658147
2064:22473295
1978:29447627
1937:30231390
1850:31273487
1815:12637487
1780:29783979
1729:10321739
1707:Oncogene
1686:Archived
1652:29024566
1644:28411145
1597:28754778
1540:33027913
1480:26977831
1409:28891842
1343:19861671
1294:26309352
1149:Research
761:14q24.3
508:fashion.
496:Genetics
261:diarrhea
220:Ovarian
209:Gastric
126:, upper
69:Oncology
42:showing
4342:adenoma
4222:Stomach
4040:D003123
3791:2933058
3703:1234904
3654:2933042
3605:3454516
3522:5901552
3456:6450737
3402:5980692
3249:4481136
3200:2847875
3092:6014333
2990:3647358
2896:7408795
2873:Cancers
2799:7034349
2686:5938532
2634:6826728
2611:Cancers
2578:5611555
2522:4781313
2471:7864494
2440:Cancers
2307:2735474
2153:9590282
2118:4244907
2110:8072530
2090:Bibcode
2056:9354786
2021:8128251
2001:Bibcode
1993:Science
1902:8252616
1771:5963021
1588:6031262
1531:7600989
1366:DynaMed
1334:4091624
1285:4541378
1220:Society
1115:ovaries
1093:Surgery
968:stomach
748:HNPCC7
728:HNPCC6
707:HNPCC3
686:HNPCC4
665:HNPCC5
536:of the
474:16-26%
459:25-60%
438:25-60%
116:stomach
4632:cystic
4525:benign
4029:114400
4026:609310
4023:120435
3947:
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3837:
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2151:
2116:
2108:
2082:Nature
2062:
2054:
2019:
1976:
1962:(11).
1935:
1900:
1856:
1848:
1813:
1778:
1768:
1727:
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1434:
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1341:
1331:
1292:
1282:
1274:
1182:, and
1113:, and
1107:uterus
733:TGFBR2
675:7-10%
642:609310
611:120435
601:Locus
545:dimers
526:cancer
471:1-11%
456:4-24%
435:4-24%
204:48-62
201:25-60
193:44-61
190:52-58
134:, and
71:
46:(in a
4903:Other
4486:Liver
4271:Lower
4190:Upper
4122:hnpcc
4012:154.1
4008:153.0
3923:Books
3561:S2CID
3304:S2CID
3138:S2CID
3088:S2CID
2850:S2CID
2740:S2CID
2661:(PDF)
2355:S2CID
2261:S2CID
2217:S2CID
2179:(PDF)
2157:S2CID
2114:S2CID
2060:S2CID
1854:S2CID
1648:S2CID
990:brain
890:(TIL)
803:EPCAM
741:3p22
699:7p22
678:2p16
657:3p21
632:2p22
624:EPCAM
592:name
577:genes
451:EPCAM
417:Gene
377:n.a.
318:risk
306:risk
294:Gene
226:42.5
223:4-12
212:6-13
132:brain
112:ovary
102:, an
89:HNPCC
4783:DKC1
4742:and
4430:Anus
4051:5812
4035:MeSH
4018:OMIM
4003:9-CM
3945:OCLC
3935:ISBN
3907:2018
3885:2018
3864:2018
3835:PMID
3796:PMID
3747:PMID
3708:PMID
3659:PMID
3633:JAMA
3610:PMID
3553:PMID
3518:PMID
3461:PMID
3407:PMID
3296:PMID
3254:PMID
3205:PMID
3157:PMID
3130:PMID
3080:PMID
3036:PMID
2995:PMID
2977:ISSN
2901:PMID
2842:PMID
2804:PMID
2732:PMID
2691:PMID
2639:PMID
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2527:PMID
2476:PMID
2458:ISSN
2412:PMID
2347:PMID
2312:PMID
2253:PMID
2209:PMID
2149:PMID
2106:PMID
2052:PMID
2017:PMID
1974:PMID
1933:PMID
1898:PMID
1880:Cell
1846:PMID
1811:PMID
1776:PMID
1725:PMID
1640:PMID
1632:ISSN
1593:PMID
1575:ISSN
1536:PMID
1518:ISSN
1476:PMID
1432:ISBN
1405:PMID
1374:2019
1339:PMID
1313:JAMA
1290:PMID
1272:ISSN
1101:and
970:and
771:MSH6
753:MLH3
712:PMS1
691:PMS2
670:MSH6
649:MLH1
618:MSH2
590:OMIM
489:15%
481:PMS2
466:MSH6
445:MSH2
430:MLH1
402:18%
399:11%
393:13%
390:46%
387:15%
383:MSH6
371:32%
368:25%
365:10%
362:17%
359:57%
355:MSH2
346:17%
340:21%
337:10%
334:43%
331:46%
327:MLH1
248:and
136:skin
4849:MSI
4127:NIH
4125:at
4086:144
3999:ICD
3993:C20
3989:C18
3980:ICD
3827:doi
3786:PMC
3778:doi
3739:doi
3735:129
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3649:PMC
3641:doi
3637:293
3600:PMC
3592:doi
3545:doi
3510:doi
3506:117
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3443:doi
3397:PMC
3389:doi
3286:doi
3282:383
3244:PMC
3236:doi
3232:372
3195:PMC
3187:doi
3122:doi
3072:doi
3026:doi
3022:116
2985:PMC
2969:doi
2961:Gut
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2881:doi
2834:doi
2830:217
2794:PMC
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2778:Gut
2722:doi
2718:175
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2673:doi
2629:PMC
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2573:PMC
2565:doi
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2509:doi
2466:PMC
2448:doi
2404:doi
2400:147
2339:doi
2302:PMC
2292:doi
2245:doi
2237:Gut
2199:hdl
2191:doi
2141:doi
2098:doi
2086:371
2044:doi
2009:doi
1997:263
1964:doi
1925:doi
1888:doi
1838:doi
1803:doi
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1715:doi
1624:doi
1620:217
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1321:doi
1317:302
1280:PMC
1262:doi
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854:PCR
846:MSI
799:MMR
405:1%
396:7%
374:5%
349:1%
343:8%
263:or
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