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 Fernández de Pierola, Luis, Mun, Jenifer, Buch, Stephan, Schafmayer, Clemens, Maiorana, Maria Valeria, Veneroni, Silvia, Van Wezel, Tom, Liu, Tao, Westers, Helga, Esteban-Jurado, Clara, Ocan, Teresa, Pique, Josep M., Andreu, Montserrat, Jover, Rodrigo, Carracedo, Angel, Xicola, Rosa, Llor, Xavier, Castells, Antoni, The EPICOLON Consortium, Dunlop15, Malcolm, Hofstra, Robert, Lindblom, Annika, Wijnen, Juul, Peterlongo, Paolo, Hampe, Jochen, Ruiz Ponte, Clara, Castellví-Bel, Sergi
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/17094
Acceso en línea:http://hdl.handle.net/10810/17094
Access Level:acceso abierto
Palabra clave:genome-wide association
lynch syndrome
susceptibility loci
hereditary
risk
identification
classification
metaanalysis
mutations
tumors
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
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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