843:(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.
43:
86:
512:
792:. 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.
796:
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.
1212:, 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.
795:
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
1223:
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
1066:
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
585:
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
784:
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
3165:
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.
1197:. 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.
3282:
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
1180:
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,
946:
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
828:(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.
1140:
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.
963:
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.
2404:
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".
4009:
3990:
286:
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
1504:
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).
972:
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:
295:
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.
2785:"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)"
1082:
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,
4737:
2245:
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".
872:, 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.
867:
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
2383:
1564:
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).
2966:
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).
4730:
291:, 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
299:
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.
1398:
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".
2045:
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".
859:). 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
4983:
5003:
4723:
1100:
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.
1839:
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".
4174:
2091:
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".
2142:
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".
851:
Mutations in DNA mismatch repair systems can lead to difficulty transmitting regions within the DNA which contain repeating patterns of two or three nucleotides (
3826:"Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic"
1096:
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.
1093:
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
2340:
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".
1016:
Amsterdam I Criteria (all bullet points must be fulfilled): The
Amsterdam I criteria were published in 1990; however, were felt to be insufficiently sensitive.
243:
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,
1021:
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
4405:
2387:
161:
1136:
Surgery remains the front-line therapy for Lynch syndrome. Patients with Lynch syndrome who develop colorectal cancer may be treated with either a partial
3489:
2002:
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".
3025:"New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC"
4113:
3186:"The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside"
2447:"Artificial Intelligence for Histology-Based Detection of Microsatellite Instability and Prediction of Response to Immunotherapy in Colorectal Cancer"
1755:"Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review"
4167:
4655:
3689:"Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds"
4515:
3357:
2566:
2510:
1714:"Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair"
1566:"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"
1164:
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
1156:
Checkpoint blockade with anti-PD-1 therapy is now preferred first line therapy for advanced Microsatellite-Instability–High colorectal cancer.
3949:
3511:
Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ (February 1966). "Hereditary factors in cancer. Study of two large midwestern kindreds".
3738:"Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability"
3737:
562:
MLH1 protein dimerizes with PMS2 protein to form MutLα, which coordinates the binding of other proteins involved with mismatch repair like
4704:
4660:
4160:
4028:
1209:
1037:
The Amsterdam II criteria were developed in 1999 and improved the diagnostic sensitivity for Lynch syndrome by including cancers of the
2835:
Ring KL, Garcia C, Thomas MH, Modesitt SC (November 2017). "Current and future role of genetic screening in gynecologic malignancies".
1446:
4778:
3825:
1963:"Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders"
1696:
1434:
4267:
813:
634:
461:
4832:
4958:
4563:
3073:
Vindigni SM, Kaz AM (April 2016). "Universal Screening of Colorectal Cancers for Lynch Syndrome: Challenges and Opportunities".
935:
and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.
816:
gene, identified by genetic testing. Candidates for germline genetic testing can be identified by clinical criteria such as the
4881:
3640:"Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X"
567:
42:
4998:
4754:
4665:
4468:
4425:
4396:
1059:
1030:
54:
4937:
4376:
3777:"Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability"
4137:
3546:
Bellizzi AM, Frankel WL (November 2009). "Colorectal cancer due to deficiency in DNA mismatch repair function: a review".
2968:"Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts"
4715:
4694:
4368:
4281:
4191:
4121:
1236:
996:
4993:
4746:
4634:
4410:
4386:
1694:
Pathology of Hereditary Nonpolyposis Colorectal Cancer - JASS 910 (1): 62 - Annals of the New York Academy of Sciences
1507:"Diagnostics of Mutations in MMR/EPCAM Genes and Their Role in the Treatment and Care of Patients with Lynch Syndrome"
1239:, AliveAndKickn, Lynch Syndrome UK and Bowel Cancer UK. In the US, National Lynch Syndrome Awareness Day is March 22.
4372:
2187:"Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome"
1926:
Yurgelun MB, Hampel H (May 2018). "Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention".
4988:
4904:
4859:
4820:
4650:
4391:
4245:
2562:"Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation"
898:
881:
856:
825:
532:
62:
4899:
4147:
2719:
Taieb, Julien; Svrcek, Magali; Cohen, Romain; Basile, Debora; Tougeron, David; Phelip, Jean-Marc (November 2022).
4558:
4487:
4183:
864:
4953:
1148:-based adjuvant therapies for Lynch syndrome-related colorectal tumours, particularly those in stages I and II.
1050:
Three or more family members with HNPCC-related cancers, one of whom is a first-degree relative of the other two
4510:
4364:
4141:
4045:
3888:
4876:
2936:
2878:
Sroczynski G, Gogollari A, Conrads-Frank A, Hallsson LR, Pashayan N, Widschwendter M, Siebert U (July 2020).
2618:"Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer"
1928:
American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting
4699:
4448:
4217:
2880:"Cost-Effectiveness of Early Detection and Prevention Strategies for Endometrial Cancer-A Systematic Review"
1227:
Complicating matters is the presence of an alternative set of criteria, known as the "Bethesda Guidelines."
1012:
The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:
956:
130:
4799:
4540:
4328:
4290:
4200:
4126:
4110:
982:
3283:
Cutsem, Eric; Yang, Ping; Farooqui, Mohammed Z.H.; Marinello, Patricia; Diaz, Luis A. (3 December 2020).
2721:"Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment"
4842:
4096:
3590:
1113:
4400:
4132:
3687:
Scott RJ, McPhillips M, Meldrum CJ, Fitzgerald PE, Adams K, Spigelman AD, et al. (January 2001).
2445:
Hildebrand, Lindsey A.; Pierce, Colin J.; Dennis, Michael; Paracha, Munizay; Maoz, Asaf (2021-01-21).
2214:
511:
4545:
3824:
Lipton LR, Johnson V, Cummings C, Fisher S, Risby P, Eftekhar Sadat AT, et al. (December 2004).
3775:
Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, RĂĽschoff J, et al. (February 2004).
2100:
2011:
1804:
Peltomäki P (March 2003). "Role of DNA mismatch repair defects in the pathogenesis of human cancer".
1165:
836:
821:
544:
263:
has also been associated with Lynch syndrome, although this relationship is not entirely understood.
248:
58:
17:
3591:"Familial colorectal cancer type X: the other half of hereditary nonpolyposis colon cancer syndrome"
1261:"Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer"
4941:
4863:
4013:
1887:"The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer"
1753:
Yokoyama T, Takehara K, Sugimoto N, Kaneko K, Fujimoto E, Okazawa-Sakai M, et al. (May 2018).
1216:
1128:
to prevent cancer from developing) can be performed before ovarian or endometrial cancer develops.
921:
840:
809:
591:
528:
252:
150:
85:
2186:
4605:
4587:
4527:
4356:
4352:
3571:
3314:
3148:
3098:
2860:
2750:
2560:
Snowsill T, Coelho H, Huxley N, Jones-Hughes T, Briscoe S, Frayling IM, Hyde C (September 2017).
2504:
Snowsill T, Huxley N, Hoyle M, Jones-Hughes T, Coelho H, Cooper C, et al. (September 2014).
2365:
2271:
2227:
2167:
2124:
2070:
1864:
1658:
1220:
1169:
960:
932:
817:
789:
524:
516:
288:
134:
118:
114:
3853:
4828:
4672:
4624:
4615:
4338:
4240:
4209:
4056:
3955:
3945:
3845:
3806:
3757:
3718:
3669:
3620:
3563:
3528:
3471:
3417:
3306:
3264:
3215:
3167:
3140:
3123:
Bui QM, Lin D, Ho W (February 2017). "Approach to Lynch Syndrome for the Gastroenterologist".
3090:
3046:
3005:
2987:
2911:
2852:
2814:
2742:
2701:
2649:
2593:
2537:
2486:
2468:
2422:
2357:
2322:
2263:
2219:
2159:
2116:
2062:
2027:
1984:
1943:
1908:
1856:
1821:
1786:
1735:
1650:
1642:
1603:
1585:
1546:
1528:
1486:
1442:
1415:
1349:
1300:
1282:
1190:
1075:
If a person meets any 1 of 5 criteria the tumour(s) from the person should be tested for MSI:
805:
555:
283:
244:
74:
1885:
Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, et al. (December 1993).
985:
cancer every 3–5 years, starting at age 30 at the earliest (preferably in a research setting)
4473:
4347:
4262:
4250:
3837:
3796:
3788:
3749:
3708:
3700:
3659:
3651:
3610:
3602:
3555:
3520:
3461:
3453:
3407:
3399:
3296:
3254:
3246:
3205:
3197:
3132:
3082:
3036:
2995:
2979:
2901:
2891:
2844:
2804:
2796:
2783:
Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, et al. (March 2020).
2732:
2691:
2683:
2639:
2629:
2583:
2575:
2527:
2519:
2476:
2458:
2414:
2349:
2312:
2302:
2255:
2209:
2201:
2151:
2108:
2054:
2019:
1974:
1935:
1898:
1848:
1813:
1776:
1766:
1725:
1634:
1593:
1577:
1536:
1518:
1407:
1339:
1331:
1318:
Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, et al. (October 2009).
1290:
1272:
1235:
There are a number of non-profit organisations providing information and support, including
1182:
4932:
4762:
4750:
4315:
4298:
4117:
1700:
1693:
1452:
1084:
947:
surveillance should then be performed at a 1-2 year interval for Lynch Syndrome patients.
894:
326:
267:
256:
154:
2668:
2506:"A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome"
1090:
Colorectal cancer with MSI-high pathology in a person who is younger than 60 years of age
909:
but researchers are trying to use artificial intelligence to predict MSI from histology.
149:. The increased risk for these cancers is due to inherited genetic mutations that impair
3909:
2767:
2185:
Ou J, Rasmussen M, Westers H, Andersen SD, Jager PO, Kooi KA, et al. (April 2009).
2104:
2015:
4948:
4927:
4849:
4629:
4592:
4522:
4420:
4360:
4303:
4232:
4222:
3801:
3776:
3713:
3688:
3664:
3639:
3615:
3466:
3441:
3412:
3387:
3259:
3234:
3233:
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. (June 2015).
3210:
3185:
3000:
2967:
2906:
2879:
2809:
2784:
2696:
2644:
2617:
2588:
2532:
2481:
2446:
2317:
2290:
1781:
1754:
1598:
1565:
1541:
1506:
1344:
1319:
1295:
1260:
1205:
1194:
1145:
1121:
989:
978:
860:
852:
571:
314:
292:
126:
122:
27:
Autosomal dominant genetic condition associated with a high risk of cancer in the colon
4022:
4018:
3041:
3024:
4977:
4921:
4837:
4573:
4255:
3638:
Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, et al. (April 2005).
3318:
2754:
1903:
1886:
1868:
943:
260:
138:
3575:
3152:
2864:
2369:
2275:
2231:
2171:
2074:
1961:
Le S, Ansari U, Mumtaz A, Malik K, Patel P, Doyle A, Khachemoune A (November 2017).
1662:
4535:
3736:
Gologan A, Krasinskas A, Hunt J, Thull DL, Farkas L, Sepulveda AR (November 2005).
3102:
2128:
1676:
1372:
1109:
554:
The 4 main genes involved in Lynch syndrome normally encode for proteins that form
275:
103:
3388:"Recent progress in Lynch syndrome and other familial colorectal cancer syndromes"
66:
4050:
3753:
3559:
3332:
2770:. From Medscape. By Juan Carlos Munoz and Louis R Lambiase. Updated: Oct 31, 2011
2418:
1411:
4891:
4600:
4553:
4496:
4440:
4080:
1621:
Ring, Kari L.; Garcia, Christine; Thomas, Martha H.; Modesitt, Susan C. (2017).
1523:
1038:
1000:
869:
320:
upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancer risk
279:
146:
142:
3524:
3457:
2983:
2848:
2800:
2737:
2720:
1852:
1638:
1581:
1474:
4811:
4788:
4686:
4085:
4061:
3959:
3606:
3201:
3136:
3086:
2353:
2307:
1771:
1186:
788:
Up to 39% of families with mutations in a Lynch syndrome gene do not meet the
548:
50:
4152:
3655:
3285:"Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer"
2991:
2472:
1646:
1589:
1532:
1286:
1277:
179:
Lifetime risk and mean age at diagnosis for Lynch syndrome–associated cancers
4582:
4505:
4323:
4148:
National Cancer Institute: Genetics of Colorectal Cancer information summary
4003:
3999:
3841:
2896:
2634:
2616:
Evrard C, Tachon G, Randrian V, Karayan-Tapon L, Tougeron D (October 2019).
2463:
2259:
2023:
1817:
1137:
906:
578:
577:
MSH2 protein dimerizes with MSH6 protein, which identifies mismatches via a
540:
3849:
3810:
3761:
3722:
3673:
3624:
3567:
3475:
3421:
3310:
3268:
3219:
3171:
3144:
3094:
3050:
3009:
2915:
2856:
2818:
2746:
2705:
2687:
2653:
2597:
2541:
2490:
2426:
2361:
2326:
2267:
2223:
1988:
1947:
1860:
1825:
1790:
1739:
1730:
1713:
1654:
1622:
1607:
1550:
1490:
1419:
1353:
1335:
1304:
905:
The histopathological criteria are not sensitive enough to detect MSI from
3792:
3532:
3301:
3284:
3250:
2163:
2120:
2066:
2031:
1912:
1623:"Current and future role of genetic screening in gynecologic malignancies"
4793:
4772:
4645:
4091:
1979:
1962:
1067:
information to help health care providers identify persons at high risk.
563:
271:
79:
2667:
Nouri Nojadeh, Jafar; Behrouz Sharif, Shahin; Sakhinia, Ebrahim (2018).
1939:
3403:
2058:
992:, starting at age 30 at the earliest (preferably in a research setting)
863:
from both a tumor tissue sample and a normal tissue sample followed by
117:
genetic condition that is associated with a high risk of colon cancer,
3982:
2205:
2155:
1880:
1878:
1219:
defect, and use the term "familial colorectal cancer type X" when the
1215:
Other sources reserve the term "Lynch syndrome" when there is a known
920:(HNPCC associated with other cancers of the gastrointestinal tract or
3994:
3867:
2579:
2561:
2523:
2505:
2112:
1117:
1056:
One or more of the HNPCC-related cancers diagnosed under age 50 years
743:
536:
3942:
Daughter of Family G. : a memoir of cancer genes, love and fate
3704:
1125:
510:
531:, which causes an elevated rate of single nucleotide changes and
4642:
4039:
4036:
4033:
3358:"Work starts on a cancer vaccine for people with Lynch syndrome"
884:– MSI) cancers can be recognized by histopathological criteria:
763:
722:
701:
680:
659:
652:
628:
621:
600:
587:
535:, also known as MSI-H (the H is "high"). MSI is identifiable in
491:
476:
455:
440:
4719:
4156:
3497:
1045:
Amsterdam Criteria II (all bullet points must be fulfilled):
3910:"CDC: March 22nd is National Lynch Syndrome Awareness Day!"
2384:"Fact Sheet 33 | BOWEL CANCER AND INHERITED PREDISPOSITION"
1320:"Risk of pancreatic cancer in families with Lynch syndrome"
543:
laboratory. Most cases result in changes in the lengths of
804:
A diagnosis of Lynch syndrome is applied to people with a
270:
and common signs and symptoms include blood in the stool,
3333:"Lynchvax: Vaccine hope for cancer risk genetic disorder"
3235:"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency"
3023:
Vasen HF, Watson P, Mecklin JP, Lynch HT (June 1999).
1172:
but clinical trials are far from being conducted yet.
1027:
One or more colon cancers diagnosed under age 50 years
839:(IHC) is a method that can be used to detect abnormal
820:
and Bethesda Guidelines, or through tumor analysis by
1473:
Braun MM, Overbeek-Wager EA, Grumbo RJ (March 2016).
527:
fashion. The hallmark of Lynch syndrome is defective
3972:
1144:
There is an ongoing controversy over the benefit of
160:
Other HNPCC conditions include Lynch-like syndrome,
4913:
4890:
4858:
4819:
4810:
4761:
4685:
4614:
4572:
4495:
4486:
4461:
4439:
4337:
4314:
4289:
4280:
4231:
4208:
4199:
4190:
4071:
3976:
1712:Oki E, Oda S, Maehara Y, Sugimachi K (March 1999).
1003:
or spinal cord), starting at age 25 at the earliest
73:
35:
1259:Carethers, John M; Stoffel, Elena M (2015-08-21).
855:), otherwise known as microsatellite instability (
3184:Boland CR, Koi M, Chang DK, Carethers JM (2007).
2669:"Microsatellite instability in colorectal cancer"
995:Annual physical and neurological exams to detect
1475:"Diagnosis and Management of Endometrial Cancer"
897:in any location showing any measurable level of
551:cytosine and adenine (sequence: CACACACACA...).
4984:DNA replication and repair-deficiency disorders
4127:GeneReviews/NCBI/NIH/UW entry on Lynch syndrome
3742:Archives of Pathology & Laboratory Medicine
3440:Biller LH, Syngal S, Yurgelun MB (April 2019).
1441:(2nd ed.). New York: McGraw-Hill Medical.
5004:Syndromes affecting the gastrointestinal tract
3386:Boland PM, Yurgelun MB, Boland CR (May 2018).
2086:
2084:
109:HNPCC includes (and was once synonymous with)
65:-H tumours, as may be seen in Lynch syndrome.
4731:
4168:
2837:American Journal of Obstetrics and Gynecology
2440:
2438:
2436:
1627:American Journal of Obstetrics and Gynecology
423:Risk of gynecologic cancer in Lynch syndrome
8:
1152:Anti-PD-1 antibody therapy can be effective.
162:polymerase proofreading-associated polyposis
4816:
4738:
4724:
4716:
4492:
4286:
4205:
4196:
4175:
4161:
4153:
3973:
3964:Paperback version retitled Before My Time.
3595:Surgical Oncology Clinics of North America
2215:11370/b74f7d2b-12fb-4bfc-a8c8-2d8950e81972
1841:International Journal of Clinical Oncology
1224:have a DNA-mismatch-repair gene mutation.
812:genes (MLH1, MSH2, MSH6, and PMS2) or the
421:
84:
41:
32:
4872:Hereditary nonpolyposis colorectal cancer
4431:Hereditary nonpolyposis colorectal cancer
3800:
3712:
3663:
3614:
3465:
3411:
3300:
3258:
3209:
3040:
2999:
2905:
2895:
2808:
2736:
2695:
2643:
2633:
2587:
2531:
2480:
2462:
2316:
2306:
2213:
1978:
1902:
1780:
1770:
1729:
1597:
1540:
1522:
1343:
1294:
1276:
1079:Colorectal cancer diagnosed before age 50
888:right-sided poorly differentiated cancers
609:Frequency of mutations in HNPCC families
266:Two-thirds of colon cancers occur in the
96:Hereditary nonpolyposis colorectal cancer
36:Hereditary nonpolyposis colorectal cancer
3781:Journal of the National Cancer Institute
1041:, small bowel, ureter and renal pelvis.
596:
301:
183:
4656:Intraductal papillary mucinous neoplasm
2768:Hereditary Colorectal Cancer Background
1248:
912:In addition, HNPCC can be divided into
164:and familial colorectal cancer type X.
2611:
2609:
2607:
2295:Hereditary Cancer in Clinical Practice
3435:
3433:
3431:
3381:
3379:
3377:
3118:
3116:
3114:
3112:
3068:
3066:
3064:
3062:
3060:
2961:
2959:
2957:
2931:
2929:
2927:
2925:
2830:
2828:
2778:
2776:
2555:
2553:
2551:
2399:
2397:
1367:
1365:
1363:
1254:
1252:
18:Hereditary non-polyposis colon cancer
7:
997:cancer in the central nervous system
581:, a protein for scanning for errors.
102:) is a hereditary predisposition to
4705:Desmoplastic small round cell tumor
3944:. Toronto: Alfred A. Knopf Canada.
3442:"Recent advances in Lynch syndrome"
3392:CA: A Cancer Journal for Clinicians
3239:The New England Journal of Medicine
1210:Creighton University Medical Center
1053:Two successive affected generations
1024:Two successive affected generations
568:single-stranded-DNA binding-protein
4406:Polymerase proofreading-associated
3693:American Journal of Human Genetics
523:Lynch syndrome is inherited in an
25:
4268:Hereditary diffuse gastric cancer
3889:"Bowel Cancer UK: Lynch Syndrome"
2289:Suchy J, Lubinski J (June 2008).
1265:World Journal of Gastroenterology
4959:Severe combined immunodeficiency
4564:Nodular regenerative hyperplasia
3362:Cancer Research UK - Cancer News
1435:"Chapter 33: Endometrial Cancer"
1400:Diseases of the Colon and Rectum
4882:Mismatch repair cancer syndrome
3289:New England Journal of Medicine
3125:Digestive Diseases and Sciences
3075:Digestive Diseases and Sciences
2194:Genes, Chromosomes & Cancer
4755:DNA repair-deficiency disorder
4666:Solid pseudopapillary neoplasm
4469:Gastrointestinal stromal tumor
4426:Familial adenomatous polyposis
3548:Advances in Anatomic Pathology
1060:Familial adenomatous polyposis
1031:Familial adenomatous polyposis
247:, ureter/renal pelvis cancer,
193:Mean age at diagnosis (years)
55:tumor-infiltrating lymphocytes
1:
4474:Krukenberg tumor (metastatic)
3513:Archives of Internal Medicine
3042:10.1016/S0016-5085(99)70510-X
880:Three major groups of MSI-H (
61:), a finding associated with
4833:DeSanctis–Cacchione syndrome
4779:Aicardi–Goutières syndrome 4
4695:Primary peritoneal carcinoma
4369:traditional serrated adenoma
4122:National Institute of Health
3830:Journal of Clinical Oncology
3754:10.5858/2005-129-1390-POTRBG
3560:10.1097/PAP.0b013e3181bb6bdc
2567:Health Technology Assessment
2511:Health Technology Assessment
2419:10.1053/j.gastro.2014.04.001
1904:10.1016/0092-8674(93)90546-3
1806:Journal of Clinical Oncology
1412:10.1097/DCR.0000000000000926
1237:Lynch Syndrome International
988:Annual urinalysis to detect
977:Upper endoscopies to detect
916:(familial colon cancer) and
891:right-sided mucinous cancers
4635:Pancreatic ductal carcinoma
1524:10.3390/diagnostics10100786
1208:, Professor of Medicine at
1071:Revised Bethesda Guidelines
818:Amsterdam Clinical Criteria
323:urinary tract cancers risk
5020:
4905:Nijmegen breakage syndrome
4821:Nucleotide excision repair
4651:Serous microcystic adenoma
4246:Signet ring cell carcinoma
4184:Digestive system neoplasia
3589:Lindor NM (October 2009).
3525:10.1001/archinte.117.2.206
3458:10.1007/s10689-018-00117-1
2984:10.1136/gutjnl-2012-304356
2849:10.1016/j.ajog.2017.04.011
2801:10.1136/gutjnl-2019-319915
2738:10.1016/j.ejca.2022.07.020
2725:European Journal of Cancer
1967:Dermatology Online Journal
1853:10.1007/s10147-019-01494-y
1639:10.1016/j.ajog.2017.04.011
1582:10.1136/gutjnl-2017-314057
951:Endometrial/ovarian cancer
899:intraepithelial lymphocyte
882:microsatellite instability
847:Microsatellite instability
826:microsatellite instability
606:Genes implicated in HNPCC
533:microsatellite instability
4938:Rothmund–Thomson syndrome
4559:Focal nodular hyperplasia
3607:10.1016/j.soc.2009.07.003
3202:10.1007/s10689-007-9145-9
3137:10.1007/s10620-016-4346-4
3087:10.1007/s10620-015-3964-6
2354:10.1007/s10689-009-9298-9
2308:10.1186/1897-4287-6-2-103
1772:10.1186/s12885-018-4489-0
1479:American Family Physician
515:HNPCC is inherited in an
49:
40:
4661:Mucinous cystic neoplasm
4511:Hepatocellular carcinoma
4365:sessile serrated adenoma
3656:10.1001/jama.293.16.1979
3356:Gunn, Tim (2024-09-09).
1278:10.3748/wjg.v21.i31.9253
586:with other mutations in
434:Endometrial cancer risk
311:endometrial cancer risk
4770:Separation/initiation:
4700:Peritoneal mesothelioma
4449:Squamous cell carcinoma
4218:Squamous cell carcinoma
3842:10.1200/JCO.2004.11.084
2937:"Medical Options | CDC"
2897:10.3390/cancers12071874
2635:10.3390/cancers11101567
2464:10.3390/cancers13030391
2260:10.1136/gut.2008.156695
2024:10.1126/science.8128251
1818:10.1200/JCO.2003.04.060
1681:Genetics Home Reference
1062:(FAP) has been excluded
1033:(FAP) has been excluded
957:transvaginal ultrasound
308:colorectal cancer risk
4800:Dyskeratosis congenita
4541:Hepatocellular adenoma
4329:Pseudomyxoma peritonei
2688:10.17179/EXCLI2017-948
1731:10.1038/sj.onc.1202583
1336:10.1001/jama.2009.1529
707:relatively infrequent
520:
121:(second most common),
4999:Syndromes with tumors
4900:Ataxia–telangiectasia
4843:Xeroderma pigmentosum
3302:10.1056/NEJMoa2017699
3251:10.1056/NEJMoa1500596
1114:salpingo-oophorectomy
806:germline DNA mutation
514:
4954:Li–Fraumeni syndrome
4546:Cavernous hemangioma
4397:Familial adenomatous
4384:Polyposis syndromes:
1980:10.5070/D32311037239
1166:University of Oxford
837:Immunohistochemistry
832:Immunohistochemistry
822:immunohistochemistry
545:dinucleotide repeats
431:Ovarian cancer risk
255:. Increased risk of
251:, brain cancer, and
249:biliary tract cancer
4942:RAPADILINO syndrome
4877:Muir–Torre syndrome
4864:DNA mismatch repair
3940:McKay, Ami (2019).
3868:"Lynch Syndrome UK"
3793:10.1093/jnci/djh034
2105:1994Natur.371...75N
2016:1994Sci...263.1625P
1940:10.1200/EDBK_208341
1439:Williams Gynecology
1433:Hoffman BL (2012).
1379:. February 22, 2019
1217:DNA mismatch repair
922:reproductive system
592:DNA mismatch repair
579:sliding clamp model
529:DNA mismatch repair
497:6% (combined risk)
424:
253:sebaceous neoplasms
151:DNA mismatch repair
135:hepatobiliary tract
4994:Hereditary cancers
4606:Gallbladder cancer
4588:Cholangiocarcinoma
4528:Liver angiosarcoma
4462:Upper and/or lower
4411:Serrated polyposis
4116:2007-08-15 at the
4072:External resources
3404:10.3322/caac.21448
2059:10.1038/ng1197-271
1699:2006-06-19 at the
1221:Amsterdam criteria
1170:Cancer Research UK
1168:with a grant from
1008:Amsterdam criteria
961:endometrial biopsy
933:Genetic counseling
790:Amsterdam criteria
671:Papadopoulos 1994
665:approximately 30%
640:approximately 60%
615:First publication
525:autosomal dominant
521:
517:autosomal dominant
422:
289:endometrial cancer
282:. The mean age of
190:Lifetime risk (%)
168:Signs and symptoms
153:. It is a type of
119:endometrial cancer
115:autosomal dominant
4989:Colorectal cancer
4971:
4970:
4967:
4966:
4829:Cockayne syndrome
4747:Metabolic disease
4713:
4712:
4681:
4680:
4673:Pancreatoblastoma
4625:exocrine pancreas
4482:
4481:
4457:
4456:
4276:
4275:
4241:Gastric carcinoma
4106:
4105:
3951:978-0-345-80946-9
3500:on July 22, 2011.
3295:(23): 2207–2218.
2206:10.1002/gcc.20644
2156:10.1038/ng0598-17
1271:(31): 9253–9261.
1191:African Americans
918:Lynch syndrome II
778:
777:
539:specimens in the
504:
503:
420:
419:
332:brain tumor risk
284:colorectal cancer
278:, and unintended
245:pancreatic cancer
241:
240:
93:
92:
59:colorectal cancer
30:Medical condition
16:(Redirected from
5011:
4817:
4740:
4733:
4726:
4717:
4493:
4392:MUTYH-associated
4377:Cronkhite–Canada
4348:Colorectal polyp
4287:
4263:Linitis plastica
4251:Gastric lymphoma
4206:
4197:
4177:
4170:
4163:
4154:
3974:
3963:
3922:
3921:
3919:
3917:
3906:
3900:
3899:
3897:
3895:
3885:
3879:
3878:
3876:
3874:
3864:
3858:
3857:
3852:. Archived from
3821:
3815:
3814:
3804:
3772:
3766:
3765:
3733:
3727:
3726:
3716:
3684:
3678:
3677:
3667:
3635:
3629:
3628:
3618:
3586:
3580:
3579:
3543:
3537:
3536:
3508:
3502:
3501:
3496:. Archived from
3494:www.oncolink.org
3486:
3480:
3479:
3469:
3437:
3426:
3425:
3415:
3383:
3372:
3371:
3369:
3368:
3353:
3347:
3346:
3344:
3343:
3329:
3323:
3322:
3304:
3279:
3273:
3272:
3262:
3230:
3224:
3223:
3213:
3181:
3175:
3163:
3157:
3156:
3120:
3107:
3106:
3070:
3055:
3054:
3044:
3029:Gastroenterology
3020:
3014:
3013:
3003:
2963:
2952:
2951:
2949:
2948:
2933:
2920:
2919:
2909:
2899:
2875:
2869:
2868:
2832:
2823:
2822:
2812:
2780:
2771:
2765:
2759:
2758:
2740:
2716:
2710:
2709:
2699:
2673:
2664:
2658:
2657:
2647:
2637:
2613:
2602:
2601:
2591:
2580:10.3310/hta21510
2557:
2546:
2545:
2535:
2524:10.3310/hta18580
2501:
2495:
2494:
2484:
2466:
2442:
2431:
2430:
2407:Gastroenterology
2401:
2392:
2391:
2386:. Archived from
2380:
2374:
2373:
2337:
2331:
2330:
2320:
2310:
2286:
2280:
2279:
2242:
2236:
2235:
2217:
2191:
2182:
2176:
2175:
2139:
2133:
2132:
2113:10.1038/371075a0
2088:
2079:
2078:
2042:
2036:
2035:
2010:(5153): 1625–9.
1999:
1993:
1992:
1982:
1958:
1952:
1951:
1923:
1917:
1916:
1906:
1882:
1873:
1872:
1836:
1830:
1829:
1801:
1795:
1794:
1784:
1774:
1750:
1744:
1743:
1733:
1709:
1703:
1691:
1685:
1684:
1677:"Lynch Syndrome"
1673:
1667:
1666:
1618:
1612:
1611:
1601:
1576:(7): 1306–1316.
1561:
1555:
1554:
1544:
1526:
1501:
1495:
1494:
1470:
1464:
1463:
1461:
1460:
1451:. Archived from
1430:
1424:
1423:
1406:(10): 999–1017.
1395:
1389:
1388:
1386:
1384:
1373:"Lynch Syndrome"
1369:
1358:
1357:
1347:
1315:
1309:
1308:
1298:
1280:
1256:
1183:French Canadians
1116:(removal of the
1085:keratoacanthomas
959:with or without
914:Lynch syndrome I
734:Nicolaides 1994
713:Nicolaides 1994
597:
590:involved in the
425:
302:
184:
89:
88:
45:
33:
21:
5019:
5018:
5014:
5013:
5012:
5010:
5009:
5008:
4974:
4973:
4972:
4963:
4933:Werner syndrome
4909:
4886:
4854:
4806:
4763:DNA replication
4757:
4751:DNA replication
4744:
4714:
4709:
4677:
4610:
4568:
4478:
4453:
4435:
4333:
4310:
4299:Duodenal cancer
4291:Small intestine
4272:
4227:
4186:
4181:
4118:Wayback Machine
4107:
4102:
4101:
4067:
4066:
3985:
3971:
3952:
3939:
3936:
3931:
3929:Further reading
3926:
3925:
3915:
3913:
3908:
3907:
3903:
3893:
3891:
3887:
3886:
3882:
3872:
3870:
3866:
3865:
3861:
3836:(24): 4934–43.
3823:
3822:
3818:
3774:
3773:
3769:
3735:
3734:
3730:
3686:
3685:
3681:
3650:(16): 1979–85.
3637:
3636:
3632:
3588:
3587:
3583:
3545:
3544:
3540:
3510:
3509:
3505:
3488:
3487:
3483:
3446:Familial Cancer
3439:
3438:
3429:
3385:
3384:
3375:
3366:
3364:
3355:
3354:
3350:
3341:
3339:
3331:
3330:
3326:
3281:
3280:
3276:
3245:(26): 2509–20.
3232:
3231:
3227:
3190:Familial Cancer
3183:
3182:
3178:
3164:
3160:
3122:
3121:
3110:
3072:
3071:
3058:
3022:
3021:
3017:
2965:
2964:
2955:
2946:
2944:
2935:
2934:
2923:
2877:
2876:
2872:
2834:
2833:
2826:
2782:
2781:
2774:
2766:
2762:
2718:
2717:
2713:
2671:
2666:
2665:
2661:
2615:
2614:
2605:
2559:
2558:
2549:
2503:
2502:
2498:
2444:
2443:
2434:
2403:
2402:
2395:
2382:
2381:
2377:
2342:Familial Cancer
2339:
2338:
2334:
2291:"MSH6 syndrome"
2288:
2287:
2283:
2254:(11): 1539–44.
2244:
2243:
2239:
2189:
2184:
2183:
2179:
2144:Nature Genetics
2141:
2140:
2136:
2099:(6492): 75–80.
2090:
2089:
2082:
2047:Nature Genetics
2044:
2043:
2039:
2001:
2000:
1996:
1960:
1959:
1955:
1934:(38): 101–109.
1925:
1924:
1920:
1884:
1883:
1876:
1847:(9): 999–1011.
1838:
1837:
1833:
1803:
1802:
1798:
1752:
1751:
1747:
1711:
1710:
1706:
1701:Wayback Machine
1692:
1688:
1675:
1674:
1670:
1620:
1619:
1615:
1563:
1562:
1558:
1503:
1502:
1498:
1472:
1471:
1467:
1458:
1456:
1449:
1432:
1431:
1427:
1397:
1396:
1392:
1382:
1380:
1371:
1370:
1361:
1317:
1316:
1312:
1258:
1257:
1250:
1245:
1233:
1203:
1178:
1162:
1134:
1122:fallopian tubes
1106:
1010:
930:
895:adenocarcinomas
878:
853:microsatellites
849:
841:mismatch repair
834:
802:
572:DNA polymerases
509:
327:prostate cancer
257:prostate cancer
187:Type of cancer
175:
170:
155:cancer syndrome
131:small intestine
83:
31:
28:
23:
22:
15:
12:
11:
5:
5017:
5015:
5007:
5006:
5001:
4996:
4991:
4986:
4976:
4975:
4969:
4968:
4965:
4964:
4962:
4961:
4956:
4951:
4949:Fanconi anemia
4946:
4945:
4944:
4935:
4930:
4928:Bloom syndrome
4917:
4915:
4911:
4910:
4908:
4907:
4902:
4896:
4894:
4888:
4887:
4885:
4884:
4879:
4874:
4868:
4866:
4856:
4855:
4853:
4852:
4850:IBIDS syndrome
4847:
4846:
4845:
4835:
4825:
4823:
4814:
4808:
4807:
4805:
4804:
4803:
4802:
4784:
4783:
4782:
4781:
4767:
4765:
4759:
4758:
4745:
4743:
4742:
4735:
4728:
4720:
4711:
4710:
4708:
4707:
4702:
4697:
4691:
4689:
4683:
4682:
4679:
4678:
4676:
4675:
4669:
4668:
4663:
4658:
4653:
4638:
4637:
4632:
4630:Adenocarcinoma
4620:
4618:
4612:
4611:
4609:
4608:
4596:
4595:
4593:Klatskin tumor
4590:
4578:
4576:
4570:
4569:
4567:
4566:
4561:
4549:
4548:
4543:
4531:
4530:
4525:
4523:Hepatoblastoma
4520:
4519:
4518:
4501:
4499:
4490:
4484:
4483:
4480:
4479:
4477:
4476:
4471:
4465:
4463:
4459:
4458:
4455:
4454:
4452:
4451:
4445:
4443:
4437:
4436:
4434:
4433:
4428:
4423:
4421:Adenocarcinoma
4414:
4413:
4408:
4403:
4394:
4389:
4380:
4379:
4343:
4341:
4335:
4334:
4332:
4331:
4326:
4320:
4318:
4312:
4311:
4309:
4308:
4307:
4306:
4304:Adenocarcinoma
4295:
4293:
4284:
4278:
4277:
4274:
4273:
4271:
4270:
4265:
4260:
4259:
4258:
4248:
4243:
4237:
4235:
4229:
4228:
4226:
4225:
4223:Adenocarcinoma
4220:
4214:
4212:
4203:
4194:
4188:
4187:
4182:
4180:
4179:
4172:
4165:
4157:
4151:
4150:
4145:
4129:
4124:
4104:
4103:
4100:
4099:
4088:
4086:Lynch Syndrome
4076:
4075:
4073:
4069:
4068:
4065:
4064:
4053:
4042:
4025:
4006:
3986:
3981:
3980:
3978:
3977:Classification
3970:
3969:External links
3967:
3966:
3965:
3950:
3935:
3932:
3930:
3927:
3924:
3923:
3901:
3880:
3859:
3856:on 2013-04-15.
3816:
3767:
3748:(11): 1390–7.
3728:
3705:10.1086/316942
3699:(1): 118–127.
3679:
3630:
3581:
3538:
3503:
3481:
3452:(2): 211–219.
3427:
3398:(3): 217–231.
3373:
3348:
3324:
3274:
3225:
3176:
3158:
3131:(2): 299–304.
3108:
3056:
3015:
2978:(6): 812–823.
2953:
2921:
2870:
2843:(5): 512–521.
2824:
2795:(3): 411–444.
2772:
2760:
2711:
2659:
2603:
2547:
2496:
2432:
2393:
2390:on 2019-02-28.
2375:
2332:
2281:
2237:
2177:
2134:
2080:
2037:
1994:
1953:
1918:
1897:(5): 1027–38.
1874:
1831:
1796:
1745:
1724:(12): 2143–7.
1704:
1686:
1668:
1633:(5): 512–521.
1613:
1556:
1496:
1465:
1448:978-0071716727
1447:
1425:
1390:
1359:
1330:(16): 1790–5.
1310:
1247:
1246:
1244:
1241:
1232:
1229:
1206:Henry T. Lynch
1202:
1199:
1195:Ashkenazi Jews
1177:
1174:
1161:
1158:
1154:
1153:
1146:5-fluorouracil
1133:
1130:
1105:
1102:
1098:
1097:
1094:
1091:
1088:
1080:
1064:
1063:
1057:
1054:
1051:
1035:
1034:
1028:
1025:
1022:
1009:
1006:
1005:
1004:
993:
990:bladder cancer
986:
929:
926:
903:
902:
892:
889:
877:
876:Classification
874:
861:DNA extraction
848:
845:
833:
830:
808:in one of the
801:
798:
785:detecting it.
776:
775:
773:
770:
767:
760:
756:
755:
753:
750:
747:
740:
736:
735:
732:
729:
726:
719:
715:
714:
711:
708:
705:
698:
694:
693:
690:
687:
684:
677:
673:
672:
669:
666:
663:
656:
648:
647:
644:
641:
638:
625:
617:
616:
613:
610:
607:
604:
583:
582:
575:
508:
505:
502:
501:
498:
495:
487:
486:
483:
480:
472:
471:
468:
465:
451:
450:
447:
444:
436:
435:
432:
429:
418:
417:
414:
411:
408:
405:
402:
399:
396:
390:
389:
386:
383:
380:
377:
374:
371:
368:
362:
361:
358:
355:
352:
349:
346:
343:
340:
334:
333:
330:
324:
321:
318:
315:ovarian cancer
312:
309:
306:
293:gastric cancer
268:proximal colon
239:
238:
235:
232:
228:
227:
224:
221:
217:
216:
213:
210:
206:
205:
202:
199:
195:
194:
191:
188:
174:
173:Risk of cancer
171:
169:
166:
111:Lynch syndrome
91:
90:
77:
71:
70:
47:
46:
38:
37:
29:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
5016:
5005:
5002:
5000:
4997:
4995:
4992:
4990:
4987:
4985:
4982:
4981:
4979:
4960:
4957:
4955:
4952:
4950:
4947:
4943:
4939:
4936:
4934:
4931:
4929:
4926:
4925:
4924:
4923:
4922:RecQ helicase
4919:
4918:
4916:
4912:
4906:
4903:
4901:
4898:
4897:
4895:
4893:
4889:
4883:
4880:
4878:
4875:
4873:
4870:
4869:
4867:
4865:
4861:
4857:
4851:
4848:
4844:
4841:
4840:
4839:
4838:Thymine dimer
4836:
4834:
4830:
4827:
4826:
4824:
4822:
4818:
4815:
4813:
4809:
4801:
4798:
4797:
4796:
4795:
4790:
4786:
4785:
4780:
4777:
4776:
4775:
4774:
4769:
4768:
4766:
4764:
4760:
4756:
4752:
4748:
4741:
4736:
4734:
4729:
4727:
4722:
4721:
4718:
4706:
4703:
4701:
4698:
4696:
4693:
4692:
4690:
4688:
4684:
4674:
4671:
4670:
4667:
4664:
4662:
4659:
4657:
4654:
4652:
4648:
4647:
4644:
4640:
4639:
4636:
4633:
4631:
4628:
4626:
4622:
4621:
4619:
4617:
4613:
4607:
4604:
4602:
4598:
4597:
4594:
4591:
4589:
4586:
4584:
4580:
4579:
4577:
4575:
4574:Biliary tract
4571:
4565:
4562:
4560:
4557:
4555:
4551:
4550:
4547:
4544:
4542:
4539:
4537:
4533:
4532:
4529:
4526:
4524:
4521:
4517:
4516:Fibrolamellar
4514:
4513:
4512:
4509:
4507:
4503:
4502:
4500:
4498:
4494:
4491:
4489:
4485:
4475:
4472:
4470:
4467:
4466:
4464:
4460:
4450:
4447:
4446:
4444:
4442:
4438:
4432:
4429:
4427:
4424:
4422:
4419:
4416:
4415:
4412:
4409:
4407:
4404:
4402:
4398:
4395:
4393:
4390:
4388:
4385:
4382:
4381:
4378:
4374:
4373:Peutz–Jeghers
4370:
4366:
4362:
4358:
4354:
4351:
4349:
4345:
4344:
4342:
4340:
4336:
4330:
4327:
4325:
4322:
4321:
4319:
4317:
4313:
4305:
4302:
4301:
4300:
4297:
4296:
4294:
4292:
4288:
4285:
4283:
4279:
4269:
4266:
4264:
4261:
4257:
4256:MALT lymphoma
4254:
4253:
4252:
4249:
4247:
4244:
4242:
4239:
4238:
4236:
4234:
4230:
4224:
4221:
4219:
4216:
4215:
4213:
4211:
4207:
4204:
4202:
4198:
4195:
4193:
4189:
4185:
4178:
4173:
4171:
4166:
4164:
4159:
4158:
4155:
4149:
4146:
4143:
4139:
4135:
4134:
4130:
4128:
4125:
4123:
4119:
4115:
4112:
4111:FAQs on HNPCC
4109:
4108:
4098:
4094:
4093:
4089:
4087:
4083:
4082:
4078:
4077:
4074:
4070:
4063:
4059:
4058:
4054:
4052:
4048:
4047:
4043:
4041:
4038:
4035:
4031:
4030:
4026:
4024:
4020:
4016:
4015:
4011:
4007:
4005:
4001:
3997:
3996:
3992:
3988:
3987:
3984:
3979:
3975:
3968:
3961:
3957:
3953:
3947:
3943:
3938:
3937:
3933:
3928:
3911:
3905:
3902:
3890:
3884:
3881:
3869:
3863:
3860:
3855:
3851:
3847:
3843:
3839:
3835:
3831:
3827:
3820:
3817:
3812:
3808:
3803:
3798:
3794:
3790:
3786:
3782:
3778:
3771:
3768:
3763:
3759:
3755:
3751:
3747:
3743:
3739:
3732:
3729:
3724:
3720:
3715:
3710:
3706:
3702:
3698:
3694:
3690:
3683:
3680:
3675:
3671:
3666:
3661:
3657:
3653:
3649:
3645:
3641:
3634:
3631:
3626:
3622:
3617:
3612:
3608:
3604:
3601:(4): 637–45.
3600:
3596:
3592:
3585:
3582:
3577:
3573:
3569:
3565:
3561:
3557:
3554:(6): 405–17.
3553:
3549:
3542:
3539:
3534:
3530:
3526:
3522:
3519:(2): 206–12.
3518:
3514:
3507:
3504:
3499:
3495:
3491:
3485:
3482:
3477:
3473:
3468:
3463:
3459:
3455:
3451:
3447:
3443:
3436:
3434:
3432:
3428:
3423:
3419:
3414:
3409:
3405:
3401:
3397:
3393:
3389:
3382:
3380:
3378:
3374:
3363:
3359:
3352:
3349:
3338:
3334:
3328:
3325:
3320:
3316:
3312:
3308:
3303:
3298:
3294:
3290:
3286:
3278:
3275:
3270:
3266:
3261:
3256:
3252:
3248:
3244:
3240:
3236:
3229:
3226:
3221:
3217:
3212:
3207:
3203:
3199:
3195:
3191:
3187:
3180:
3177:
3173:
3169:
3162:
3159:
3154:
3150:
3146:
3142:
3138:
3134:
3130:
3126:
3119:
3117:
3115:
3113:
3109:
3104:
3100:
3096:
3092:
3088:
3084:
3081:(4): 969–76.
3080:
3076:
3069:
3067:
3065:
3063:
3061:
3057:
3052:
3048:
3043:
3038:
3035:(6): 1453–6.
3034:
3030:
3026:
3019:
3016:
3011:
3007:
3002:
2997:
2993:
2989:
2985:
2981:
2977:
2973:
2969:
2962:
2960:
2958:
2954:
2942:
2938:
2932:
2930:
2928:
2926:
2922:
2917:
2913:
2908:
2903:
2898:
2893:
2889:
2885:
2881:
2874:
2871:
2866:
2862:
2858:
2854:
2850:
2846:
2842:
2838:
2831:
2829:
2825:
2820:
2816:
2811:
2806:
2802:
2798:
2794:
2790:
2786:
2779:
2777:
2773:
2769:
2764:
2761:
2756:
2752:
2748:
2744:
2739:
2734:
2730:
2726:
2722:
2715:
2712:
2707:
2703:
2698:
2693:
2689:
2685:
2681:
2677:
2676:EXCLI Journal
2670:
2663:
2660:
2655:
2651:
2646:
2641:
2636:
2631:
2627:
2623:
2619:
2612:
2610:
2608:
2604:
2599:
2595:
2590:
2585:
2581:
2577:
2574:(51): 1–238.
2573:
2569:
2568:
2563:
2556:
2554:
2552:
2548:
2543:
2539:
2534:
2529:
2525:
2521:
2518:(58): 1–406.
2517:
2513:
2512:
2507:
2500:
2497:
2492:
2488:
2483:
2478:
2474:
2470:
2465:
2460:
2456:
2452:
2448:
2441:
2439:
2437:
2433:
2428:
2424:
2420:
2416:
2413:(2): 502–26.
2412:
2408:
2400:
2398:
2394:
2389:
2385:
2379:
2376:
2371:
2367:
2363:
2359:
2355:
2351:
2348:(2): 141–50.
2347:
2343:
2336:
2333:
2328:
2324:
2319:
2314:
2309:
2304:
2300:
2296:
2292:
2285:
2282:
2277:
2273:
2269:
2265:
2261:
2257:
2253:
2249:
2241:
2238:
2233:
2229:
2225:
2221:
2216:
2211:
2207:
2203:
2200:(4): 340–50.
2199:
2195:
2188:
2181:
2178:
2173:
2169:
2165:
2161:
2157:
2153:
2149:
2145:
2138:
2135:
2130:
2126:
2122:
2118:
2114:
2110:
2106:
2102:
2098:
2094:
2087:
2085:
2081:
2076:
2072:
2068:
2064:
2060:
2056:
2052:
2048:
2041:
2038:
2033:
2029:
2025:
2021:
2017:
2013:
2009:
2005:
1998:
1995:
1990:
1986:
1981:
1976:
1972:
1968:
1964:
1957:
1954:
1949:
1945:
1941:
1937:
1933:
1929:
1922:
1919:
1914:
1910:
1905:
1900:
1896:
1892:
1888:
1881:
1879:
1875:
1870:
1866:
1862:
1858:
1854:
1850:
1846:
1842:
1835:
1832:
1827:
1823:
1819:
1815:
1812:(6): 1174–9.
1811:
1807:
1800:
1797:
1792:
1788:
1783:
1778:
1773:
1768:
1764:
1760:
1756:
1749:
1746:
1741:
1737:
1732:
1727:
1723:
1719:
1715:
1708:
1705:
1702:
1698:
1695:
1690:
1687:
1682:
1678:
1672:
1669:
1664:
1660:
1656:
1652:
1648:
1644:
1640:
1636:
1632:
1628:
1624:
1617:
1614:
1609:
1605:
1600:
1595:
1591:
1587:
1583:
1579:
1575:
1571:
1567:
1560:
1557:
1552:
1548:
1543:
1538:
1534:
1530:
1525:
1520:
1516:
1512:
1508:
1500:
1497:
1492:
1488:
1485:(6): 468–74.
1484:
1480:
1476:
1469:
1466:
1455:on 2014-01-04
1454:
1450:
1444:
1440:
1436:
1429:
1426:
1421:
1417:
1413:
1409:
1405:
1401:
1394:
1391:
1378:
1374:
1368:
1366:
1364:
1360:
1355:
1351:
1346:
1341:
1337:
1333:
1329:
1325:
1321:
1314:
1311:
1306:
1302:
1297:
1292:
1288:
1284:
1279:
1274:
1270:
1266:
1262:
1255:
1253:
1249:
1242:
1240:
1238:
1230:
1228:
1225:
1222:
1218:
1213:
1211:
1207:
1200:
1198:
1196:
1192:
1188:
1184:
1175:
1173:
1171:
1167:
1159:
1157:
1151:
1150:
1149:
1147:
1142:
1139:
1131:
1129:
1127:
1123:
1119:
1115:
1111:
1108:Prophylactic
1103:
1101:
1095:
1092:
1089:
1086:
1081:
1078:
1077:
1076:
1073:
1072:
1068:
1061:
1058:
1055:
1052:
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968:Other cancers
965:
962:
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945:
944:Colonoscopies
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4787:Termination/
4771:
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4430:
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4383:
4357:hyperplastic
4346:
4339:Colon/rectum
4131:
4090:
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4055:
4044:
4027:
4008:
3989:
3941:
3914:. Retrieved
3912:. 2018-03-20
3904:
3892:. Retrieved
3883:
3871:. Retrieved
3862:
3854:the original
3833:
3829:
3819:
3787:(4): 261–8.
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3498:the original
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3361:
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3340:. Retrieved
3336:
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2943:. 2020-04-01
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2053:(3): 271–2.
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1997:
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1457:. Retrieved
1453:the original
1438:
1428:
1403:
1399:
1393:
1383:November 18,
1381:. Retrieved
1376:
1327:
1323:
1313:
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1264:
1234:
1226:
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1179:
1176:Epidemiology
1163:
1155:
1143:
1135:
1110:hysterectomy
1107:
1099:
1074:
1070:
1069:
1065:
1044:
1043:
1036:
1015:
1014:
1011:
971:
967:
966:
954:
950:
949:
942:
939:Colon cancer
938:
937:
931:
917:
913:
911:
904:
879:
850:
835:
803:
794:
787:
781:
780:People with
779:
762:
749:case report
742:
728:case report
721:
700:
692:Miyaki 1997
679:
658:
646:Fishel 1993
633:
627:
584:
564:DNA helicase
553:
522:
490:
475:
460:
454:
439:
393:
365:
337:
298:
276:constipation
265:
242:
209:Endometrial
178:
177:
176:
159:
110:
108:
104:colon cancer
99:
95:
94:
4892:MRN complex
4601:gallbladder
4554:hyperplasia
4081:GeneReviews
3337:www.bbc.com
2941:www.cdc.gov
2890:(7): 1874.
2731:: 136–157.
2682:: 159–168.
2150:(1): 17–8.
1517:(10): 786.
1511:Diagnostics
1201:Terminology
1039:endometrium
983:small bowel
870:immunoscore
570:(RPA), and
549:nucleobases
280:weight loss
198:Colorectal
4978:Categories
4812:DNA repair
4789:telomerase
4687:Peritoneum
4057:DiseasesDB
3960:1089450897
3490:"Oncolink"
3367:2024-09-18
3342:2024-09-18
2947:2020-12-07
2457:(3): 391.
1765:(1): 576.
1759:BMC Cancer
1459:2014-06-23
1243:References
1187:Icelanders
824:(IHC), or
51:Micrograph
4646:neoplasms
4583:bile duct
4506:malignant
4488:Accessory
4418:Neoplasm:
4401:Gardner's
4324:Carcinoid
4210:Esophagus
4144:GeneTests
4120:from the
3319:227259533
2992:0017-5749
2755:252289107
2473:2072-6694
1869:195795805
1647:1097-6868
1590:1468-3288
1533:2075-4418
1287:1007-9327
1138:colectomy
1132:Treatment
928:Screening
907:histology
800:Diagnosis
769:disputed
731:2q31-q33
651:HNPCC2 (
620:HNPCC1 (
594:pathway:
541:pathology
75:Specialty
4773:RNASEH2A
4616:Pancreas
4387:Juvenile
4361:juvenile
4316:Appendix
4192:GI tract
4114:Archived
4092:Orphanet
3916:31 March
3894:31 March
3873:31 March
3850:15611508
3811:14970275
3762:16253017
3723:11112663
3674:15855431
3625:19793571
3576:25600795
3568:19851131
3476:30627969
3422:29485237
3311:33264544
3269:26028255
3220:17636426
3172:31378807
3153:32833106
3145:27990589
3095:26602911
3051:10348829
3010:23408351
2916:32664613
2865:29024566
2857:28411145
2819:31780574
2747:36115290
2706:29743854
2654:31618962
2598:28895526
2542:25244061
2491:33494280
2427:25043945
2370:25479413
2362:19851887
2327:19804606
2276:10608978
2268:18625694
2232:15526044
2224:19156873
2172:46658147
2075:22473295
1989:29447627
1948:30231390
1861:31273487
1826:12637487
1791:29783979
1740:10321739
1718:Oncogene
1697:Archived
1663:29024566
1655:28411145
1608:28754778
1551:33027913
1491:26977831
1420:28891842
1354:19861671
1305:26309352
1160:Research
772:14q24.3
519:fashion.
507:Genetics
272:diarrhea
231:Ovarian
220:Gastric
137:, upper
80:Oncology
53:showing
4353:adenoma
4233:Stomach
4051:D003123
3802:2933058
3714:1234904
3665:2933042
3616:3454516
3533:5901552
3467:6450737
3413:5980692
3260:4481136
3211:2847875
3103:6014333
3001:3647358
2907:7408795
2884:Cancers
2810:7034349
2697:5938532
2645:6826728
2622:Cancers
2589:5611555
2533:4781313
2482:7864494
2451:Cancers
2318:2735474
2164:9590282
2129:4244907
2121:8072530
2101:Bibcode
2067:9354786
2032:8128251
2012:Bibcode
2004:Science
1913:8252616
1782:5963021
1599:6031262
1542:7600989
1377:DynaMed
1345:4091624
1296:4541378
1231:Society
1126:ovaries
1104:Surgery
979:stomach
759:HNPCC7
739:HNPCC6
718:HNPCC3
697:HNPCC4
676:HNPCC5
547:of the
485:16-26%
470:25-60%
449:25-60%
127:stomach
4643:cystic
4536:benign
4040:114400
4037:609310
4034:120435
3958:
3948:
3848:
3809:
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2127:
2119:
2093:Nature
2073:
2065:
2030:
1987:
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1911:
1867:
1859:
1824:
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1352:
1342:
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1293:
1285:
1193:, and
1124:, and
1118:uterus
744:TGFBR2
686:7-10%
653:609310
622:120435
612:Locus
556:dimers
537:cancer
482:1-11%
467:4-24%
446:4-24%
215:48-62
212:25-60
204:44-61
201:52-58
145:, and
82:
57:(in a
4914:Other
4497:Liver
4282:Lower
4201:Upper
4133:hnpcc
4023:154.1
4019:153.0
3934:Books
3572:S2CID
3315:S2CID
3149:S2CID
3099:S2CID
2861:S2CID
2751:S2CID
2672:(PDF)
2366:S2CID
2272:S2CID
2228:S2CID
2190:(PDF)
2168:S2CID
2125:S2CID
2071:S2CID
1865:S2CID
1659:S2CID
1001:brain
901:(TIL)
814:EPCAM
752:3p22
710:7p22
689:2p16
668:3p21
643:2p22
635:EPCAM
603:name
588:genes
462:EPCAM
428:Gene
388:n.a.
329:risk
317:risk
305:Gene
237:42.5
234:4-12
223:6-13
143:brain
123:ovary
113:, an
100:HNPCC
4794:DKC1
4753:and
4441:Anus
4062:5812
4046:MeSH
4029:OMIM
4014:9-CM
3956:OCLC
3946:ISBN
3918:2018
3896:2018
3875:2018
3846:PMID
3807:PMID
3758:PMID
3719:PMID
3670:PMID
3644:JAMA
3621:PMID
3564:PMID
3529:PMID
3472:PMID
3418:PMID
3307:PMID
3265:PMID
3216:PMID
3168:PMID
3141:PMID
3091:PMID
3047:PMID
3006:PMID
2988:ISSN
2912:PMID
2853:PMID
2815:PMID
2743:PMID
2702:PMID
2650:PMID
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2538:PMID
2487:PMID
2469:ISSN
2423:PMID
2358:PMID
2323:PMID
2264:PMID
2220:PMID
2160:PMID
2117:PMID
2063:PMID
2028:PMID
1985:PMID
1944:PMID
1909:PMID
1891:Cell
1857:PMID
1822:PMID
1787:PMID
1736:PMID
1651:PMID
1643:ISSN
1604:PMID
1586:ISSN
1547:PMID
1529:ISSN
1487:PMID
1443:ISBN
1416:PMID
1385:2019
1350:PMID
1324:JAMA
1301:PMID
1283:ISSN
1112:and
981:and
782:MSH6
764:MLH3
723:PMS1
702:PMS2
681:MSH6
660:MLH1
629:MSH2
601:OMIM
500:15%
492:PMS2
477:MSH6
456:MSH2
441:MLH1
413:18%
410:11%
404:13%
401:46%
398:15%
394:MSH6
382:32%
379:25%
376:10%
373:17%
370:57%
366:MSH2
357:17%
351:21%
348:10%
345:43%
342:46%
338:MLH1
259:and
147:skin
4860:MSI
4138:NIH
4136:at
4097:144
4010:ICD
4004:C20
4000:C18
3991:ICD
3838:doi
3797:PMC
3789:doi
3750:doi
3746:129
3709:PMC
3701:doi
3660:PMC
3652:doi
3648:293
3611:PMC
3603:doi
3556:doi
3521:doi
3517:117
3462:PMC
3454:doi
3408:PMC
3400:doi
3297:doi
3293:383
3255:PMC
3247:doi
3243:372
3206:PMC
3198:doi
3133:doi
3083:doi
3037:doi
3033:116
2996:PMC
2980:doi
2972:Gut
2902:PMC
2892:doi
2845:doi
2841:217
2805:PMC
2797:doi
2789:Gut
2733:doi
2729:175
2692:PMC
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2576:doi
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2459:doi
2415:doi
2411:147
2350:doi
2313:PMC
2303:doi
2256:doi
2248:Gut
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2202:doi
2152:doi
2109:doi
2097:371
2055:doi
2020:doi
2008:263
1975:doi
1936:doi
1899:doi
1849:doi
1814:doi
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1726:doi
1635:doi
1631:217
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1340:PMC
1332:doi
1328:302
1291:PMC
1273:doi
924:).
865:PCR
857:MSI
810:MMR
416:1%
407:7%
385:5%
360:1%
354:8%
274:or
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