{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:20:15Z","timestamp":1781907615574,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p &lt; 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1\/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.<\/jats:p>","DOI":"10.3390\/jcm9061861","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:50:49Z","timestamp":1592268649000},"page":"1861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Spectrum and Frequency of Tumors, Cancer Risk and Survival in Chilean Families with Lynch Syndrome: Experience of the Implementation of a Registry"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5349-0267","authenticated-orcid":false,"given":"Karin","family":"\u00c1lvarez","sequence":"first","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Orellana","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0577-7604","authenticated-orcid":false,"given":"Marjorie","family":"De la Fuente","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Canales","sequence":"additional","affiliation":[{"name":"Cancer Institute, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Pinto","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Heine","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"},{"name":"Colorectal Unit, Department of Surgery, Hospital San Jos\u00e9, Osorno 5311523, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Solar","sequence":"additional","affiliation":[{"name":"Genetic Section, University of Chile Clinic Hospital, Santiago 8380456, Chile"},{"name":"Servicio de Neurolog\u00eda Infantil, Hospital de Puerto Montt, Puerto Montt 5507798, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0067-8383","authenticated-orcid":false,"given":"Claudia","family":"Hurtado","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e5l","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, 0369 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Kronberg","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro Jos\u00e9","family":"Zarate","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"},{"name":"Department of Surgery, Finis Terrae University, Santiago 7501015, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7856-0057","authenticated-orcid":false,"given":"Mev","family":"Dominguez-Valentin","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, 0369 Oslo, Norway"},{"name":"Instituto de Investigaci\u00f3n, Universidad Cat\u00f3lica de Trujillo, Chimbote 02800, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"L\u00f3pez-K\u00f6stner","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Genetic Laboratory, Coloproctology Unit, Cl\u00ednica Las Condes, Santiago 7591047, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"(2020, May 14). Departamento de Estad\u00edsticas de Informaci\u00f3n de Salud. Available online: www.deis.minsal.cl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1463-1318.2012.03110.x","article-title":"Increasing crude and adjusted mortality rates for colorectal cancer in a developing South American country","volume":"15","author":"Zarate","year":"2013","journal-title":"Colorectal Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1001\/jama.293.16.1986","article-title":"Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer","volume":"293","author":"Pinol","year":"2005","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"v78","DOI":"10.1093\/annonc\/mdq169","article-title":"Familial colorectal cancer risk: ESMO Clinical Practice Guidelines","volume":"21","author":"Balmana","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/ng.2854","article-title":"Application of a 5-tiered scheme for standardized classification of 2360 unique mismatch repair gene variants in the InSiGHT locus-specific database","volume":"46","author":"Thompson","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s11894-012-0280-6","article-title":"Familial colon cancer syndromes: An update of a rapidly evolving field","volume":"14","author":"Patel","year":"2012","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1056\/NEJMra012242","article-title":"Hereditary colorectal cancer","volume":"348","author":"Lynch","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/humu.21446","article-title":"Recurrence and variability of germline EPCAM deletions in Lynch syndrome","volume":"32","author":"Kuiper","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1136\/gutjnl-2015-309675","article-title":"Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: First report from the prospective Lynch syndrome database","volume":"66","author":"Moller","year":"2017","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1136\/gutjnl-2016-311403","article-title":"Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: A report from the prospective Lynch syndrome database","volume":"66","author":"Moller","year":"2017","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/ng.3247","article-title":"Large-scale whole-genome sequencing of the Icelandic population","volume":"47","author":"Gudbjartsson","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1136\/gutjnl-2017-314057","article-title":"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","volume":"67","author":"Moller","year":"2018","journal-title":"Gut"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dominguez-Valentin, M., Joost, P., Therkildsen, C., Jonsson, M., Rambech, E., and Nilbert, M. (2016). Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urol., 16.","DOI":"10.1186\/s12894-016-0130-1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.urology.2015.08.018","article-title":"Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations","volume":"86","author":"Joost","year":"2015","journal-title":"Urology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s10689-014-9744-1","article-title":"High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry","volume":"13","author":"Rosty","year":"2014","journal-title":"Fam. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1158\/1078-0432.CCR-09-3058","article-title":"Lynch syndrome-associated breast cancers: Clinicopathologic characteristics of a case series from the colon cancer family registry","volume":"16","author":"Walsh","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/DCR.0b013e3181d0c114","article-title":"Spectrum of MLH1 and MSH2 mutations in Chilean families with suspected Lynch syndrome","volume":"53","author":"Alvarez","year":"2010","journal-title":"Dis. Colon Rectum"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1007\/s10350-007-9037-y","article-title":"Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) in Argentina: Report from a referral hospital register","volume":"50","author":"Vaccaro","year":"2007","journal-title":"Dis. Colon Rectum"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1897-4287-11-18","article-title":"Mutation spectrum in South American Lynch syndrome families","volume":"11","author":"Nilbert","year":"2013","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Carneiro da Silva, F., Ferreira, J.R., Torrezan, G.T., Figueiredo, M.C., Santos, E.M., Nakagawa, W.T., Brianese, R.C., Petrolini de Oliveira, L., Begnani, M.D., and Aguiar-Junior, S. (2015). Clinical and molecular characterization of brazilian patients suspected to have lynch syndrome. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139753"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s10689-010-9373-2","article-title":"Frequency of extracolonic tumors in Brazilian families with Lynch syndrome: Analysis of a hereditary colorectal cancer institutional registry","volume":"9","author":"Santos","year":"2010","journal-title":"Fam. Cancer"},{"key":"ref_23","first-page":"41","article-title":"Frequency of extra-colonic tumors in hereditary nonpolyposis colorectal cancer (HNPCC) and familial colorectal cancer (FCC) Brazilian families: An analysis by a Brazilian Hereditary Colorectal Cancer Institutional Registry","volume":"3","author":"Rossi","year":"2004","journal-title":"Fam. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1136\/gutjnl-2012-304356","article-title":"Revised guidelines for the clinical management of Lynch syndrome (HNPCC): Recommendations by a group of European experts","volume":"62","author":"Vasen","year":"2013","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1053\/j.gastro.2014.04.001","article-title":"Guidelines on genetic evaluation and management of Lynch syndrome: A consensus statement by the US Multi-Society Task Force on colorectal cancer","volume":"147","author":"Giardiello","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/BF02053699","article-title":"The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC)","volume":"34","author":"Vasen","year":"1991","journal-title":"Dis. Colon Rectum"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0016-5085(99)70510-X","article-title":"New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC","volume":"116","author":"Vasen","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1093\/jnci\/89.23.1758","article-title":"A National cancer institute workshop on hereditary nonpolyposis colorectal cancer syndrome: Meeting highlights and Bethesda guidelines","volume":"89","author":"Boland","year":"1997","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djh034","article-title":"Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability","volume":"96","author":"Umar","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.4067\/S0034-98872012000900005","article-title":"Lynch syndrome: Selection of families by microsatellite instability and immunohistochemistry","volume":"140","author":"Wielandt","year":"2012","journal-title":"Rev. Med. Chil."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rossi, B.M., Palmero, E.I., Lopez-Kostner, F., Sarroca, C., Vaccaro, C.A., Spirandelli, F., Ashton-Prolla, P., Rodriguez, Y., de Campos Reis Galvao, H., and Reis, R.M. (2017). A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3599-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1053\/j.gastro.2008.04.026","article-title":"The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations","volume":"135","author":"Senter","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ejca.2019.07.017","article-title":"A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres\/registries","volume":"119","author":"Rossi","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10689-016-9882-8","article-title":"Update on Lynch syndrome genomics","volume":"15","author":"Peltomaki","year":"2016","journal-title":"Fam. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41436-019-0596-9","article-title":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: Findings from the Prospective Lynch Syndrome Database","volume":"22","author":"Sampson","year":"2020","journal-title":"Genet. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1158\/1055-9965.EPI-08-0301","article-title":"Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1914 individuals undergoing clinical genetic testing in the United States","volume":"17","author":"Kastrinos","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jso.23413","article-title":"Excess of extracolonic non-endometrial multiple primary cancers in MSH2 germline mutation carriers over MLH1","volume":"108","author":"Yheulon","year":"2013","journal-title":"J. Surg. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10689-012-9534-6","article-title":"Cancer spectrum in DNA mismatch repair gene mutation carriers: Results from a hospital based Lynch syndrome registry","volume":"11","author":"Pande","year":"2012","journal-title":"Fam. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.1200\/JCO.2001.19.20.4074","article-title":"MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: A study of hereditary nonpolyposis colorectal cancer families","volume":"19","author":"Vasen","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1399-0004.2008.01125.x","article-title":"Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: A report of 121 families with proven mutations","volume":"75","author":"Barrow","year":"2009","journal-title":"Clin. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/jnci\/djs351","article-title":"Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome","volume":"104","author":"Win","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/gim.2017.254","article-title":"MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer","volume":"20","author":"Roberts","year":"2018","journal-title":"Genet. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1093\/jnci\/djs525","article-title":"Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome","volume":"105","author":"Win","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1136\/jmedgenet-2015-103216","article-title":"Lynch syndrome caused by MLH1 mutations is associated with an increased risk of breast cancer: A cohort study","volume":"52","author":"Harkness","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R90","DOI":"10.1186\/bcr3205","article-title":"Breast carcinoma and Lynch syndrome: Molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases","volume":"14","author":"Lotsari","year":"2012","journal-title":"Breast Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.18632\/oncotarget.27538","article-title":"Does breast carcinoma belong to the Lynch syndrome tumor spectrum?\u2014Somatic mutational profiles vs. ovarian and colorectal carcinomas","volume":"11","author":"Porkka","year":"2020","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1158\/1055-9965.EPI-06-0514","article-title":"Gastric cancer is related to early Helicobacter pylori infection in a high-prevalence country","volume":"16","author":"Ferreccio","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Saita, C., Yamaguchi, T., Horiguchi, S.I., Yamada, R., Takao, M., Iijima, T., Wakaume, R., Aruga, T., Tabata, T., and Koizumi, K. (2018). Tumor development in Japanese patients with Lynch syndrome. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195572"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1001\/jama.2009.1529","article-title":"Risk of pancreatic cancer in families with Lynch syndrome","volume":"302","author":"Kastrinos","year":"2009","journal-title":"JAMA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.7150\/jca.20750","article-title":"Pancreatic Cancer in Lynch Syndrome Patients","volume":"8","author":"Bujanda","year":"2017","journal-title":"J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/ijc.23508","article-title":"The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome","volume":"123","author":"Watson","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1158\/1055-9965.EPI-09-0058","article-title":"Germ-line mutations in mismatch repair genes associated with prostate cancer","volume":"18","author":"Grindedal","year":"2009","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1136\/jmg.2010.076992","article-title":"Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers","volume":"47","author":"Kiemeney","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1200\/JCO.2012.43.2278","article-title":"Risks of less common cancers in proven mutation carriers with lynch syndrome","volume":"30","author":"Engel","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1053\/j.gastro.2005.11.032","article-title":"Decrease in mortality in Lynch syndrome families because of surveillance","volume":"130","author":"Hendriks","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/(SICI)1097-0142(19980715)83:2<259::AID-CNCR9>3.0.CO;2-L","article-title":"Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members","volume":"83","author":"Watson","year":"1998","journal-title":"Cancer"},{"key":"ref_57","first-page":"417","article-title":"Favorable survival associated with microsatellite instability in endometrioid endometrial cancers","volume":"97","author":"Maxwell","year":"2001","journal-title":"Obstet. Gynecol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pinero, T.A., Soukarieh, O., Rolain, M., Alvarez, K., Lopez-Kostner, F., Torrezan, G.T., Carraro, D.M., De Oliveira Nascimento, I.L., Bomfim, T.F., and Machado-Lopes, T.M.B. (2020). MLH1 intronic variants mapping to + 5 position of splice donor sites lead to deleterious effects on RNA splicing. Fam. Cancer.","DOI":"10.1007\/s10689-020-00182-5"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1861\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:39:02Z","timestamp":1760175542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,15]]},"references-count":58,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["jcm9061861"],"URL":"https:\/\/doi.org\/10.3390\/jcm9061861","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,15]]}}}