The MLH1 c.1852_1853delinsGC (p.K618A) variant in colorectal cancer: genetic association study in 18,723 individuals.

Colorectal 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...

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Detalles Bibliográficos
Autores: Abulí, Anna, Bujanda, Luis, Muñoz, Jenifer, Buch, Stephan, Schafmayer, Clemens, Maiorana, Maria Valeria, Veneroni, Silvia, Van Wezel, Tom, Liu, Tao, Westers, Helga, Esteban-Jurado, Clara, Ocaña, Teresa, Piqué, J. M. (Piqué Badía), Andreu, Montserrat, Jover, Rodrigo, Carracedo Álvarez, Ángel, Llor, Xavier, Castells Garangou, Antoni, Dunlop, Malcolm, Hofstra, Robert, Lindblom, Annika, Xicola, Rosa, Wijnen, Juul, Peterlongo, Paolo, Hampe, Jochen, Ruiz-Ponte, Clara, Castellví Bel, Sergi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/122275
Acceso en línea:https://hdl.handle.net/2445/122275
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Genètica molecular
Malalties hereditàries
Epidemiologia
Colorectal cancer
Molecular genetics
Genetic diseases
Epidemiology
Descripción
Sumario:Colorectal 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.

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