2026-04-20T03:27:30Zhttps://recercat.cat/oai/request

oai:recercat.cat:10459.1/483822025-02-03T08:01:30Zcom_2072_3622col_2072_479130

Meta-analysis of mismatch repair polymorphisms within the cogent consortium for colorectal cancer susceptibility Picelli, Simone Bermejo, Justo Lorenzo Chang-Claude, Jenny Hoffmeister, Michael Fernández-Rozadilla, Ceres Carracedo, Angel Castells, Antoni Castellví-Bel, Sergi Naccarati, Alessio Pardini, Barbara Vodickova, Ludmila Müller, Heiko Talseth-Palmer, Bente A. Stibbard, Geoffrey Peterlongo, Paolo Nici, Carmela Veneroni, Silvia Li, Li Casey, Graham Tenesa, Albert Farrington, Susan M. Tomlinson, Ian Moreno, Víctor Van Wezel, Tom Wijnen, Juul Dunlop, Malcolm Radice, Paolo Scott, Rodney J. Vodicka, Pavel Ruiz-Ponte, Clara Brenner, Hermann Buch, Stephan Völzke, Henry Hampe, Jochen Schafmayer, Clemens Lindblom, Annika In the last four years, Genome-Wide Association Studies (GWAS) have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC). Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a followup of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimated recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H), decreased from 1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to 1.08 in the initial meta-analysis. Since the corresponding summary probability value was 0.06, we decided to retrieve additional information for this polymorphism. The incorporation of six further studies resulted in around 13000 cases and 13000 controls. The newly updated OR was 1.03. The results from the present large, multicenter study illustrate the possibility of decreasing effect sizes with increasing samples sizes. Phenotypic heterogeneity, differential environmental exposures, and population specific linkage disequilibrium patterns may explain the observed difference of genetic effects between Sweden and the other investigated cohorts. 2015-06-26T11:17:51Z 2015-06-26T11:17:51Z 2013 article publishedVersion https://doi.org/10.1371/journal.pone.0072091 1932-6203 http://hdl.handle.net/10459.1/48382 eng Reproducció del document publicat a https://doi.org/10.1371/journal.pone.0072091 PLoS One, 2013, vol. 8, núm. 9, e72091 cc-by, (c) Picelli et al., 2013 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/3.0/es/ Public Library of Science