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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990597/ https://www.ncbi.nlm.nih.gov/pubmed/24743384 http://dx.doi.org/10.1371/journal.pone.0095022 |
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author | 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 |
author_facet | 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 |
author_sort | Abulí, Anna |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3990597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39905972014-04-21 The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals 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 PLoS One Research Article 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. Public Library of Science 2014-04-17 /pmc/articles/PMC3990597/ /pubmed/24743384 http://dx.doi.org/10.1371/journal.pone.0095022 Text en © 2014 Abulí et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals |
title | The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals |
title_full | The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals |
title_fullStr | The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals |
title_full_unstemmed | The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals |
title_short | The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals |
title_sort | mlh1 c.1852_1853delinsgc (p.k618a) variant in colorectal cancer: genetic association study in 18,723 individuals |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990597/ https://www.ncbi.nlm.nih.gov/pubmed/24743384 http://dx.doi.org/10.1371/journal.pone.0095022 |
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