Details

Autor(en) / Beteiligte

• Abulí, Anna
• Bujanda, Luis
• Muñoz, Jenifer
• Buch, Stephan
• Schafmayer, Clemens
• Valeria Maiorana, Maria
• Veneroni, Silvia
• van Wezel, Tom
• Liu, Tao
• Westers, Helga
• Esteban-Jurado, Clara
• Ocaña, Teresa
• Piqué, Josep M
• Andreu, Montserrat
• Jover, Rodrigo
• Carracedo, Angel
• Xicola, Rosa M
• Llor, Xavier
• Castells, Antoni
• Dunlop, Malcolm
• Hofstra, Robert
• Lindblom, Annika
• Wijnen, Juul
• Peterlongo, Paolo
• Hampe, Jochen
• Ruiz-Ponte, Clara
• Castellví-Bel, Sergi
• Ellis, Nathan A.

Titel

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

Ist Teil von

• PloS one, 2014-04, Vol.9 (4), p.e95022

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.