Lynch Syndrome

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Written2001-09Pierre Laurent-Puig
Laboratoire de Toxicologie Moléculaire U490, 45 rue des Saints Pères, 75006 Paris, France
Updated2017-09Maria Teresa Ricci
Hereditary Digestive Tract Tumours Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy;
Abstract Lynch syndrome (LS) is an autosomal-dominant disease characterized by an increased cancer susceptibility, particularly of the colon and endometrium. LS is caused by a constitutional heterozygous loss-of-function mutation or epimutation in one of the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2). Loss of MMR activity leads to an accumulation of DNA replication errors, especially in repetitive sequences, a phenomenon referred to as microsatellite instability (MSI). MSI occurs in the majority of LS cancers and is a hallmark of the disease. The lifetime risk of cancers in individuals with LS varies dependent on gender and on which MMR gene is mutated. Intensive colorectal screening is proven to be effective in reducing colorectal cancer-related mortality in LS patients.

Keyword Lynch syndrome, Hereditary Non-polyposis Colorectal cancer, Colorectal cancer, HNPCC, MMR, Mismatch repair

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1. Identity

Other namesHereditary Non-polyposis Colorectal Cancer, HNPCC
Atlas_Id 10049
Note Inherited cancer susceptibility syndrome characterized by a high risk of developing colorectal, endometrial and other malignancies.
Inheritance Autosomal dominant with incomplete penetrance and variable expressivity; the cumulative lifetime risk of cancers is gender-related and dependent on which MMR gene is mutated. The prevalence of LS has been estimated between one in 370 and one in 3.100 people of the general population (Stormorken et al., 2007; Jarvinen et al., 2009).

2. Clinics

Note The term Lynch Syndrome is correctly applied to families and patients with a germline defect in one of the MMR genes; this designation is more appropriate than HNPCC (Hereditary Non-Polyposis Colorectal Cancer) because LS patients could develop also some colorectal polyps, which makes the word "nonpolyposis" ambiguous.
The MMR pathway normally maintains fidelity of the DNA during replication by correction of single base pair mismatches and small insertion or deletion loops (Kunkel and Erie, 2005). LS-related cancers form when a somatic loss of the remaining wild type allele occurs; this results in loss of MMR activity and subsequent MSI in tumour tissue. The MSI, as well as the negative immunohistochemical staining for the protein encoded by the mutated MMR gene, occurs in over 90% of LS-related cancers.
Phenotype and clinics Colorectal cancer(CRC) is the most common malignancy in LS patients. LS-associated CRCs are characterized by an early age of onset (44-61 years versus 69 years in sporadic cases (Giardiello et al., 2014)); this earlier presentation is related to a more rapid adenoma-carcinoma sequence. Moreover, CRCs in LS patients frequently occur on the right side of the colon (Lynch et al., 1993; Lynch and Smyrk, 1996; Aarnio et al., 1999) and tend to be mucinous, poorly differentiated and with tumour-infiltrating lymphocytes (Kastrinos and Stoffel, 2014). Noteworthy, a high rate of metachronous CRCs after segmental colectomy has been described with a cumulative risk of 16% at 10 years and 41% at 20 years (Parry et al., 2011).
Endometrial carcinoma (EC) is the second most frequent cancer occurring in women with LS and is characterized by a young age at onset, with an average age at diagnosis of 48 years compared with 62 years in sporadic EC (Vasen et al., 2014; Hampel et al., 2005).
LS patients are also predisposed to $ (generally intestinal-type) and ovarian cancer (particularly with endometrioid / clear cell histology), with a mean age at diagnosis of 56 and 42.5 years, respectively (Aarnio et al., 1997; Capelle et al., 2010; Watson et al., 2008; Helder-Woolderink et al., 2016).
Less common LS-related malignancies include those of the urinary tract ( transitional cell carcinomas), small bowel, hepatobiliary tract, glioblastomas and cutaneous sebaceous neoplasms (Bonadona et al., 2011; Kohlmann and Gruber, 2014).
Differential diagnosis Familial CRC. This definition is used to describe families characterized by a cluster of CRCs not apparently related to a known hereditary CRC syndrome. Familial CRC is a heterogeneous condition that can be caused in part by a combination of genetic and environmental factors.
Attenuated familial adenomatous polyposis (AFAP). The attenuated form of APC-related polyposis is characterized by fewer polyps and later age of onset than classic FAP. Extracolonic manifestations (e.g., gastric and duodenal polyps, , dental anomalies, congenital hypertrophy of the retinal pigment epithelium and desmoid tumours) could be variably present. Polyps and CRCs associated with AFAP do not exhibit MSI
MUTYH-Associated polyposis (MAP). The colonic phenotype of MAP can be similar to attenuated FAP but the inheritance is autosomal recessive. A minority of individuals with MAP presented with CRC and few or no polyps (Croitoru et al., 2004: Farrington et al., 2005; Balaguer et al., 2007; Cleary et al., 2009).
Hamartomatous polyposis syndromes. These conditions are characterized by an increased risk of CRC but can be recognized by the presence of hamartomatous polyps and extracolonic manifestations.
Hereditary diffuse gastric cancer. CDH1-related gastric cancers are typically diffuse or with signet-ring histology.
BRCA1/BRCA2 hereditary breast-ovarian cancer. This condition should be suspected when the personal and/or family history includes ovarian cancer.
Neoplastic risk In MLH1 and MSH2 gene mutation carriers, the lifetime risk of CRC ranges from 30% to 74% (Giardiello, 2014). Lower risk for CRC has been estimated in patients with MSH6 and PMS2 mutation, ranging from 10% to 22% (Hendriks et al., 2004; Senter et al., 2008).
EC occurs in up to 70% of women with MSH6 mutations; lower risks are described in those with MLH1 and MSH2 mutations (54%) and with PMS2 mutations (15%) (Giardiello et al., 2014; Hendriks et al., 2004; Senter et al., 2008).
Concerning ovarian cancer, the reported lifetime risks in women with LS range from 6.7% to 12% and appear to be higher for carriers of MSH2 mutations (Watson et al., 2008; Engel et al., 2012; Bonadona et al., 2011).
Gastric cancer is reported to occur in approximately 5%-13% of LS patients, with considerable variability based on country of origin (Watson et al., 2008; Capelle et al., 2010).
The risk for other LS-related cancers is lower, though increased over general population rates.
Treatment Colorectal surveillance is the only surveillance protocol proved to be effective in LS patients. Colonoscopy is recommended every one to two years beginning between ages 20 and 25 years or two to five years before the earliest age of diagnosis in the family, whichever is earlier (Giardiello et al., 2014; NCCN, 2017). Screening for CRC by colonoscopy has been shown to decrease CRC-related mortality by 72% (Dove-Edwin et al., 2005) and has been associated with lower risk of CRC and an earlier stage at diagnosis (Parry et al., 2011; Vasen et a., 2010; Engel et al., 2010; Stuckless et al., 2012).
The evidence for efficacy of surveillance for cancer of the endometrium, ovary, stomach, duodenum and urinary tract is limited.
Prophylactic removal of the colon is generally not recommended for individuals with LS because routine colonoscopy is an effective preventive measure. If a CRC is detected, full colectomy with ileorectal anastomosis might be considered because of the high risk for metachronous cancers. Prophylactic removal of the uterus and ovaries can be considered after childbearing is completed.
Growing but not conclusive evidence exists on the use of aspirin for prevention of cancer in LS patients (Burn et al., 2011; Rothwell et al., 2011). The potential benefits, risks and current limitations of available uncertainties of aspirin therapy should be discussed with LS patients.
Prognosis Colonoscopic surveillance with early detection and treatment of invasive CRC is associated with excellent survival (Moller et al., 2015). When matched stage for stage, LS CRCs are associated with a better prognosis compared with sporadic CRCs (Watson et al., 1998; Gryfe et al., 2000).
LS-related EC or ovarian cancer have also a good prognosis when given current treatment (Moller et al., 2015).

3. Genes involved and Proteins

Gene NameMLH1 (mutL homolog 1)
Location 3p22.2
Transcription The transcribed mRNA has 2524 bps. 12 distinct transcripts have been described.
Description Size: 756 aminoacids; Molecular Mass: 84,601 Da. It contains an ATPase domain and three interaction domains, one for MutS homologs, one for PMS2, MLH3 or PMS1 and the other for EXO1.
Expression Ubiquitous
Localisation Nucleoplasm
Function The MLH1 protein dimerizes with PMS2 protein to form MutL alpha, a component of the post-replicative DNA mismatch repair (MMR) system. The MutL alpha heterodimer possesses an endonucleolytic activity that is activated following the recognition of DNA mismatches and insertion/deletion loops by MutS alpha (composed of MSH2 and MSH6) or MutS beta (composed of MSH2 and MSH3). MutL-MutS complex is responsible for the recruitment of other proteins involved in MMR.
The MLH1 protein can also bind to PMS1 or MLH3 to form MutL beta and MutL gamma respectively. MutL beta and gamma heterodimers are probably components of the MMR system.
Homology MLH1 is homolog of the E. coli DNA mismatch repair gene mutL and MLH1 homologs are also present in eukaryotes.
Germinal More than 200 different pathogenic variants have been reported. MLH1 mutations are responsible of 35-40% cases of Lynch Syndrome (LS). Nonsense, missense and splice-site mutations predominate, whereas large genomic rearrangements constitute A and exon 16 deletion account for 50% of LS families in Finland) (Lynch et al., 2009).
Somatic The most frequent cause of microsatellite instability (MSI) and loss of MLH1 and PMS2 immunohistochemical expression is the somatic methylation of the promoter region of MLH1 that silences gene expression in the tumour tissue.

Gene NameMSH2 (mutS homolog 2)
Location 2p21-p16.3
Transcription The transcribed mRNA has 3145 bps. 9 distinct transcripts have been described.
Description Size: 934 aminoacids; Molecular Mass: 104,743 Da. It contains a DNA binding domain and two interaction domains, one for MSH3 or MSH6 and the other for MutL homologs (composed of MLH1 and PMS2).
Expression Ubiquitous
Localisation Nucleoplasm.
Function The MSH2 protein forms an heterodimer with either MSH6 (MutS alpha) or MSH3 (MutS beta) and identifies DNA mismatches. While MutS alpha complex recognizes single base mismatches and dinucleotide insertion-deletion loops in the DNA, MutS beta recognizes larger insertion-deletion loops. A sliding clamp model has been suggested to describe the structure of these heterodimers. After mismatch binding, MutS alpha or beta associates with the MutL alpha heterodimer (composed of MLH1 and PMS2): MutL-MutS complex is responsible for the recruitment of other proteins involved in MMR.
Homology MSH2 is homolog of the E. coli DNA mismatch repair gene mutS and MSH2 homologs are also present in eukaryotes.
Germinal More than 170 different pathogenic variants have been reported. MSH2 mutations are responsible of 44-48% cases of Lynch Syndrome (LS). Nonsense, missense and splice-site mutations predominate, but large genomic rearrangements constitute >20% of the alterations. The higher proportion of Alu repeats may contribute to the higher rate of genomic rearrangements in MSH2 than in MLH1. There are also MSH2 founder mutations which account for a high proportion of LS families in some specific populations (e.g. exons 1-6 deletion in United States) (Lynch et al., 2009).
Somatic Microsatellite instability (MSI) and loss of MSH2 and MSH6 immunohistochemical expression can also be due to somatic mutations in MSH2 gene.

Gene NameMSH6 (mutS homolog 6)
Location 2p16.3
Transcription The transcribed mRNA has 4263 bps. 10 distinct transcripts have been described.
Description Size: 1360 aminoacids; Molecular Mass: 152,786 Da. It contains a highly conserved helix-turn-helix domain associated with a Walker-A motif (an adenine nucleotide and magnesium binding motif) with ATPase activity.
Expression Ubiquitous
Localisation Nucleoplasm
Function The MSH6 protein dimerizes with MSH2 to form MutS alpha and functions in the identifications of single base mismatches and dinucleotide insertion-deletion loops in the DNA by a sliding clamp model.
MutS alpha associates with the MutL alpha heterodimer (composed of MLH1 and PMS2): MutL-MutS complex is responsible for the recruitment of other proteins involved in MMR.
Homology MSH6 is homolog of the E. coli DNA mismatch repair gene mutS and MSH6 homologs are also present in eukaryotes.
Germinal More than 30 different pathogenic variants have been reported. MSH6 mutations are responsible of 8-10% of cases of Lynch Syndrome. Nonsense, missense and splice-site mutations predominate, whereas large genomic rearrangements are rare.
Somatic The involvement of somatic or epigenetic inactivation of MSH6 is rare.

Gene NamePMS2 (PMS1 homolog 2, mismatch repair system component)
Location 7p22.1
Transcription The transcribed mRNA has 2771 bps. 3 distinct transcripts have been described.
Pseudogene Multiple pseudogenes have been identified at 7p22, 7p12-13 and 7q11 (Nicolaides et al., 1995).
Description Size: 862 aminoacids; Molecular Mass: 95,797 Da. It contains a region of homology with other MutS or MutL homologs, comprising a region of 150 aminoacids encompassing a putative helix-turn-helix domain associated with an adenine nucleotide and magnesium binding sites.
Expression Ubiquitous.
Localisation Nucleoplasm.
Function The PMS2 protein dimerizes with MLH1 to form MutL alpha, a component of the post-replicative DNA mismatch repair (MMR) system. The MutL alpha heterodimer possesses an endonucleolytic activity that is activated following the recognition of DNA mismatches and insertion/deletion loop by MutS alpha (composed of MSH2 and MSH6) or MutS beta (composed of MSH2 and MSH3). MutL-MutS complex is responsible for the recruitment of other proteins involved in MMR.
Homology The PMS2 gene is homolog to yeast mutator gene (bacterial mutL) and PMS2 homologs are also present in eukaryotes.
Germinal Germline pathogenic variants in PMS2 are rare and are responsible of 2-8% cases of Lynch Syndrome. Single nucleotide variants and large gene rearrangements have been reported. Large rearrangements may constitute >20% of the alterations.
Somatic The involvement of somatic or epigenetic inactivation of PMS2 is rare.

Gene NameEPCAM (tumor-associated calcium signal transducer 1)
Alias ESA; KSA; M4S1; MK-1; DIAR5; EGP-2; EGP40; KS1/4; MIC18; TROP1; EGP314; HNPCC8; TACSTD1.
Location 2p21
Transcription The transcribed mRNA has 1731 bps. 3 distinct transcripts have been described.
Pseudogene One pseudogene in 4q34.3.
Description Size: 314 aminoacids; Molecular Mass: 34,932 Da. It contains a thyroglobulin type 1 repeat, two epidermal growth factor-like extracellular domains, one single transmembrane domain, one small intercellular domain (EpICD), that alone is sufficient to induce proliferation signals and PDZ-domain identified in its C-terminal end.
Expression Highly and selectively expressed by undifferentiated rather than differentiated embryonic stem cells. Levels rapidly diminish as soon as embryonic stem cells differentiate. Expressed in almost all epithelial cell membranes but not on mesodermal or neural cell membranes (Litvinov et al., 1996).
Localisation Plasma membrane; baso-lateral in normal cells; redistribution on entire plasma membrane in vitro and in carcinoma cells.
Function This gene encodes a carcinoma-associated antigen and functions as a hemophilic calcium-independent cell adhesion molecule. EPCAM plays also a role in embryonic stem cell proliferation and differentiation.
Homology EPCAM homologs are also present in eukaryotes.
Germinal Deletions involving the transcription termination signal of EPCAM can lead to inactivation of the MSH2 promoter through hypermethylation and, therefore, are a rare cause of Lynch Syndrome. Other EPCAM pathogenic variants that do not affect the transcription termination signal cause autosomal recessive congenital tufting enteropathy.

4. Bibliography

Cancer risk in mutation carriers of DNA-mismatch-repair genes
Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomäki P, Mecklin JP, Järvinen HJ
Int J Cancer 1999 Apr 12;81(2):214-8
PMID 10188721
Identification of MYH mutation carriers in colorectal cancer: a multicenter, case-control, population-based study
Balaguer F, Castellví-Bel S, Castells A, Andreu M, Muñoz J, Gisbert JP, Llor X, Jover R, de Cid R, Gonzalo V, Bessa X, Xicola RM, Pons E, Alenda C, Payá A, Piqué JM; Gastrointestinal Oncology Group of the Spanish Gastroenterological Association
Clin Gastroenterol Hepatol 2007 Mar;5(3):379-87
PMID 17368238
Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome
Bonadona V, Bonaïti B, Olschwang S, Grandjouan S, Huiart L, Longy M, Guimbaud R, Buecher B, Bignon YJ, Caron O, Colas C, Noguès C, Lejeune-Dumoulin S, Olivier-Faivre L, Polycarpe-Osaer F, Nguyen TD, Desseigne F, Saurin JC, Berthet P, Leroux D, Duffour J, Manouvrier S, Frébourg T, Sobol H, Lasset C, Bonaïti-Pellié C; French Cancer Genetics Network
JAMA 2011 Jun 8;305(22):2304-10
PMID 21642682
Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial
Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard ML, Dunlop MG, Ho JW, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJ, Vasen HF, Barker G, Crawford G, Elliott F, Movahedi M, Pylvanainen K, Wijnen JT, Fodde R, Lynch HT, Mathers JC, Bishop DT; CAPP2 Investigators
Lancet 2011 Dec 17;378(9809):2081-7
PMID 22036019
Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands
Capelle LG, Van Grieken NC, Lingsma HF, Steyerberg EW, Klokman WJ, Bruno MJ, Vasen HF, Kuipers EJ
Gastroenterology 2010 Feb;138(2):487-92
PMID 19900449
Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study
Cleary SP, Cotterchio M, Jenkins MA, Kim H, Bristow R, Green R, Haile R, Hopper JL, LeMarchand L, Lindor N, Parfrey P, Potter J, Younghusband B, Gallinger S
Gastroenterology 2009 Apr;136(4):1251-60
PMID 19245865
Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk
Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S
J Natl Cancer Inst 2004 Nov 3;96(21):1631-4
PMID 15523092
Prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: 16 year, prospective, follow-up study
Dove-Edwin I, Sasieni P, Adams J, Thomas HJ
BMJ 2005 Nov 5;331(7524):1047
PMID 16243849
Risks of less common cancers in proven mutation carriers with lynch syndrome
Engel C, Loeffler M, Steinke V, Rahner N, Holinski-Feder E, Dietmaier W, Schackert HK, Goergens H, von Knebel Doeberitz M, Goecke TO, Schmiegel W, Buettner R, Moeslein G, Letteboer TG, Gómez García E, Hes FJ, Hoogerbrugge N, Menko FH, van Os TA, Sijmons RH, Wagner A, Kluijt I, Propping P, Vasen HF
J Clin Oncol 2012 Dec 10;30(35):4409-15
PMID 23091106
Efficacy of annual colonoscopic surveillance in individuals with hereditary nonpolyposis colorectal cancer
Engel C, Rahner N, Schulmann K, Holinski-Feder E, Goecke TO, Schackert HK, Kloor M, Steinke V, Vogelsang H, Möslein G, Görgens H, Dechant S, von Knebel Doeberitz M, Rüschoff J, Friedrichs N, Büttner R, Loeffler M, Propping P, Schmiegel W; German HNPCC Consortium
Clin Gastroenterol Hepatol 2010 Feb;8(2):174-82
PMID 19835992
Germline susceptibility to colorectal cancer due to base-excision repair gene defects
Farrington SM, Tenesa A, Barnetson R, Wiltshire A, Prendergast J, Porteous M, Campbell H, Dunlop MG
Am J Hum Genet 2005 Jul;77(1):112-9
PMID 15931596
Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer
Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR, Lieberman DA, Robertson DJ, Syngal S, Rex DK
Am J Gastroenterol 2014 Aug;109(8):1159-79
PMID 25070057
De novo constitutional MLH1 epimutations confer early-onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one
Goel A, Nguyen TP, Leung HC, Nagasaka T, Rhees J, Hotchkiss E, Arnold M, Banerji P, Koi M, Kwok CT, Packham D, Lipton L, Boland CR, Ward RL, Hitchins MP
Int J Cancer 2011 Feb 15;128(4):869-78
PMID 20473912
Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer
Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, Redston M, Gallinger S
N Engl J Med 2000 Jan 13;342(2):69-77
PMID 10631274
Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance
Hendriks YM, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F, Sandkuijl L, Møller P, Genuardi M, Van Houwelingen H, Tops C, Van Puijenbroek M, Verkuijlen P, Kenter G, Van Mil A, Meijers-Heijboer H, Tan GB, Breuning MH, Fodde R, Wijnen JT, Bröcker-Vriends AH, Vasen H
Gastroenterology 2004 Jul;127(1):17-25
PMID 15236168
Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation
Hitchins MP
Fam Cancer 2016 Jul;15(3):413-22
PMID 26886015
Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members
Järvinen HJ, Renkonen-Sinisalo L, Aktán-Collán K, Peltomäki P, Aaltonen LA, Mecklin JP
J Clin Oncol 2009 Oct 1;27(28):4793-7
PMID 19720893
History, genetics, and strategies for cancer prevention in Lynch syndrome
Kastrinos F, Stoffel EM
Clin Gastroenterol Hepatol 2014 May;12(5):715-27; quiz e41-3
PMID 23891921
Lynch Syndrome
Kohlmann W, Gruber SB
2004 Feb 5 [updated 2014 May 22] In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mefford HC, Stephens K, Amemiya A, Ledbetter N, editors
PMID 20301390
DNA mismatch repair
Kunkel TA, Erie DA
Annu Rev Biochem 2005;74:681-710
PMID 15952900
Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins
Litvinov SV, Balzar M, Winter MJ, Bakker HA, Briaire-de Bruijn IH, Prins F, Fleuren GJ, Warnaar SO
J Cell Biol 1997 Dec 1;139(5):1337-48
PMID 9382878
Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications
Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR
Clin Genet 2009 Jul;76(1):1-18
PMID 19659756
Hereditary nonpolyposis colorectal cancer (Lynch syndrome)
Lynch HT, Smyrk T
An updated review Cancer
PMID 8826936
Møller P, Seppälä T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons R, Jeffries J, Vasen H, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen J, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Frayling IM, Plazzer JP, Pylvanainen K, Sampson JR, Capella G, Mecklin JP, Möslein G; Mallorca Group (http://mallorca-group
Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database Gut
PMID 26657901
Genomic organization of the human PMS2 gene family
Nicolaides NC, Carter KC, Shell BK, Papadopoulos N, Vogelstein B, Kinzler KW
Genomics 1995 Nov 20;30(2):195-206
PMID 8586419
Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery
Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, Baron JA, Giles GG, Leggett BA, Winship I, Lipton L, Young GP, Young JP, Lodge CJ, Southey MC, Newcomb PA, Le Marchand L, Haile RW, Lindor NM, Gallinger S, Hopper JL, Jenkins MA
Gut 2011 Jul;60(7):950-7
PMID 21193451
Epigenetic mechanisms in the pathogenesis of Lynch syndrome
Peltomäki P
Clin Genet 2014 May;85(5):403-12
PMID 24443998
Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials
Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW
Lancet 2011 Jan 1;377(9759):31-41
PMID 21144578
The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations
Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, Lindblom A, Lagerstedt K, Thibodeau SN, Lindor NM, Young J, Winship I, Dowty JG, White DM, Hopper JL, Baglietto L, Jenkins MA, de la Chapelle A
Gastroenterology 2008 Aug;135(2):419-28
PMID 18602922
Prevention of colorectal cancer by colonoscopic surveillance in families with hereditary colorectal cancer
Stormorken AT, Clark N, Grindedal E, Maehle L, Møller P
Scand J Gastroenterol 2007 May;42(5):611-7
PMID 17454882
Impact of colonoscopic screening in male and female Lynch syndrome carriers with an MSH2 mutation
Stuckless S, Green JS, Morgenstern M, Kennedy C, Green RC, Woods MO, Fitzgerald W, Cox J, Parfrey PS
Clin Genet 2012 Nov;82(5):439-45
PMID 22011075
One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome
Vasen HF, Abdirahman M, Brohet R, Langers AM, Kleibeuker JH, van Kouwen M, Koornstra JJ, Boot H, Cats A, Dekker E, Sanduleanu S, Poley JW, Hardwick JC, de Vos Tot Nederveen Cappel WH, van der Meulen-de Jong AE, Tan TG, Jacobs MA, Mohamed FL, de Boer SY, van de Meeberg PC, Verhulst ML, Salemans JM, van Bentem N, Westerveld BD, Vecht J, Nagengast FM
Gastroenterology 2010 Jun;138(7):2300-6
PMID 20206180
Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members
Watson P, Lin KM, Rodriguez-Bigas MA, Smyrk T, Lemon S, Shashidharan M, Franklin B, Karr B, Thorson A, Lynch HT
Cancer 1998 Jul 15;83(2):259-66
PMID 9669808
The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome
Watson P, Vasen HFA, Mecklin JP, Bernstein I, Aarnio M, Järvinen HJ, Myrhøj T, Sunde L, Wijnen JT, Lynch HT
Int J Cancer 2008 Jul 15;123(2):444-449
PMID 18398828

5. Citation

This paper should be referenced as such :
Maria Teresa Ricci
Lynch Syndrome
Atlas Genet Cytogenet Oncol Haematol. 2018;22(5):220-226.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Laurent-Puig, P. Hereditary non polyposis colorectal carcinoma (HNPCC syndrome). Atlas Genet Cytogenet Oncol Haematol. 2002;6(1):56-57.

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