Abulí, AnnaBujanda, LuisMuñoz, JeniferBuch, StephanSchafmayer, ClemensMaiorana, Maria ValeriaVeneroni, SilviaVan Wezel, TomLiu, TaoWesters, HelgaEsteban-Jurado, ClaraOcaña, TeresaPiqué, J. M. (Piqué Badía)Andreu, MontserratJover, RodrigoCarracedo Álvarez, ÁngelLlor, XavierCastells Garangou, AntoniDunlop, MalcolmHofstra, RobertLindblom, AnnikaXicola, RosaWijnen, JuulPeterlongo, PaoloHampe, JochenRuiz-Ponte, ClaraCastellví Bel, Sergi2018-05-102018-05-102014-04-171932-6203https://hdl.handle.net/2445/122275Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.6 p.application/pdfengcc-by (c) Abulí, Anna et al., 2014http://creativecommons.org/licenses/by/3.0/esCàncer colorectalGenètica molecularMalalties hereditàriesEpidemiologiaColorectal cancerMolecular geneticsGenetic diseasesEpidemiologyinfo:eu-repo/semantics/article6448762018-05-10info:eu-repo/semantics/openAccess24743384