{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T20:01:51Z","timestamp":1759694511160},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T00:00:00Z","timestamp":1397692800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0095022","type":"journal-article","created":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T20:51:36Z","timestamp":1397767896000},"page":"e95022","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals"],"prefix":"10.1371","volume":"9","author":[{"given":"Anna","family":"Abul\u00ed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Bujanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenifer","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Buch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"Schafmayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Valeria Maiorana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Veneroni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"van Wezel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga","family":"Westers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Esteban-Jurado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Oca\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep M.","family":"Piqu\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Andreu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Jover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel","family":"Carracedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa M.","family":"Xicola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Llor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoni","family":"Castells","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The EPICOLON Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"Dunlop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Hofstra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Lindblom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juul","family":"Wijnen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Peterlongo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Hampe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Ruiz-Ponte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergi","family":"Castellv\u00ed-Bel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1053\/j.gastro.2010.01.054","article-title":"Hereditary and familial colon cancer","volume":"138","author":"KW Jasperson","year":"2010","journal-title":"Gastroenterology"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1002\/humu.22168","article-title":"Pathological assessment of mismatch repair gene variants in Lynch syndrome: past, present, and future","volume":"33","author":"LJ Rasmussen","year":"2012","journal-title":"Hum Mutat"},{"key":"ref3","first-page":"557","article-title":"LOVD v.2.0: the next generation in gene variant databases","volume":"32","author":"IF Fokkema","year":"2011","journal-title":"Hum Mutat 2011"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1002\/humu.20735","article-title":"Accurate classification of MLH1\/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR)","volume":"29","author":"EC Chao","year":"2008","journal-title":"Hum Mutat"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1002\/humu.20796","article-title":"A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects","volume":"29","author":"I Tournier","year":"2008","journal-title":"Hum Mutat"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/ijc.10240","article-title":"Prevalence of germline mutations of MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer families from Spain","volume":"98","author":"T Caldes","year":"2002","journal-title":"Int J Cancer"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s004390051127","article-title":"Missense mutations in hMLH1 associated with colorectal cancer","volume":"105","author":"T Liu","year":"1999","journal-title":"Hum Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/GIM.0b013e3182011489","article-title":"Integrated analysis of unclassified variants in mismatch repair genes","volume":"13","author":"C Pastrello","year":"2011","journal-title":"Genet Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"4595","DOI":"10.1158\/0008-5472.CAN-06-3509","article-title":"Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays","volume":"67","author":"M Takahashi","year":"2007","journal-title":"Cancer Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1158\/1078-0432.CCR-12-3299","article-title":"Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis","volume":"19","author":"I Hinrichsen","year":"2013","journal-title":"Clin Cancer Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/ng.2854","article-title":"Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database","volume":"46","year":"2014","journal-title":"Nat Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nrg2574","article-title":"New insights into the aetiology of colorectal cancer from genome-wide association studies","volume":"10","author":"A Tenesa","year":"2009","journal-title":"Nat Rev Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ng.670","article-title":"Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33","volume":"42","author":"RS Houlston","year":"2010","journal-title":"Nat Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e1002105","DOI":"10.1371\/journal.pgen.1002105","article-title":"Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer","volume":"7","author":"IP Tomlinson","year":"2011","journal-title":"PLoS Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/ng.2293","article-title":"Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk","volume":"44","author":"MG Dunlop","year":"2012","journal-title":"Nat Genet"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/bjc.2012.329","article-title":"The TERT variant rs2736100 is associated with colorectal cancer risk","volume":"107","author":"B Kinnersley","year":"2012","journal-title":"Br J Cancer"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/1471-2164-14-55","article-title":"A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12","volume":"14","author":"C Fern\u00e1ndez-Rozadilla","year":"2013","journal-title":"BMC Genomics 26"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/ng.2505","article-title":"Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer","volume":"45","author":"WH Jia","year":"2013","journal-title":"Nat Genet"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1053\/j.gastro.2012.12.020","article-title":"Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis","volume":"144","author":"U Peters","year":"2013","journal-title":"Gastroenterology"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e72091","DOI":"10.1371\/journal.pone.0072091","article-title":"Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility","volume":"8","author":"S Picelli","year":"2013","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/sj.bjc.6605338","article-title":"COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer","volume":"102","author":"IP Tomlinson","year":"2010","journal-title":"Br J Cancer"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/mutage\/ger059","article-title":"COGENT (COlorectal cancer GENeTics) revisited","volume":"27","author":"COGENT Houlston RS; members of","year":"2012","journal-title":"Mutagenesis"},{"key":"ref23","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":"V Pi\u00f1ol","year":"2005","journal-title":"JAMA"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1158\/1055-9965.EPI-09-0601","article-title":"Enrichment of low penetrance susceptibility loci in a Dutch familial colorectal cancer cohort","volume":"18","author":"A Middeldorp","year":"2009","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref26","first-page":"887","article-title":"Wigginton, JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy-Weinberg equilibrium","volume":"76(5)","journal-title":"Am J Hum Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1471-2350-9-52","article-title":"The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population","volume":"9","author":"LL Christensen","year":"2008","journal-title":"BMC Med Genet 11"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1471-2350-12-12","article-title":"Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome","volume":"12","author":"A Castillejo","year":"2011","journal-title":"BMC Med Genet"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jmoldx.2012.01.006","article-title":"The germline MLH1 K618A variant and susceptibility to Lynch syndrome-associated tumors","volume":"14","author":"F Medeiros","year":"2012","journal-title":"J Mol Diagn"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0095022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T20:22:24Z","timestamp":1588969344000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0095022"}},"subtitle":[],"editor":[{"given":"Nathan A.","family":"Ellis","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,4,17]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,4,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0095022","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2014,4,17]]}}}