63303 20180518103753.0 doi 10.1371/journal.pone.0072091 sideral 82821 ART-2013-82821 eng Picelli, S. Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility 2013 Access copy available to the general public Unrestricted 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 follow-up 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. info:eu-repo/grantAgreement/ES/FIS/CP-03-0070 info:eu-repo/grantAgreement/ES/FIS FEDER/PS09-02368 info:eu-repo/grantAgreement/ES/FIS FEDER/08-0024 info:eu-repo/grantAgreement/ES/FIS FEDER/08-1276 info:eu-repo/grantAgreement/ES/FIS FEDER/11-00219 info:eu-repo/grantAgreement/ES/FIS FEDER/11-00681 info:eu-repo/grantAgreement/ES/FIS/PI08-1635 info:eu-repo/grantAgreement/ES/FIS/PS09-1037 info:eu-repo/grantAgreement/ES/MICINN/SAF2010-19273 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.534 2013 MULTIDISCIPLINARY SCIENCES 8 / 56 = 0.143 2013 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Lorenzo Bermejo, J. Chang Claude, J. Hoffmeister, M. Fernández Rozadilla, C. Carracedo, A. Castells, A. Castellví Bel, S. Juan, D.M. Raquel, M. Marisa, M. Francisco, C. Jose, D. Carolina, I. Guadalupe, L. Alberto, I. Antoni, C. Virgínia, P. Sergi, C.B. Balaguer, F. Victoria, G. Teresa, O. María Dolores, G. Maria, P. Anna, S. Leticia, M. Miriam, C. Josep, M.P. (orcid)0000-0001-5932-2889 Lanas, A. Universidad de Zaragoza (orcid)0000-0001-6522-6682 Alcedo, J. (orcid)0000-0002-3869-8235 Ortego, F.J. Universidad de Zaragoza Joaquin, C. Ma, S.D. Mercedes, S. Eloy, S. Mariano, V. Montserrat, A. Anna, A. Xavier, B. Mar, I. Agustín, S. Felipe, B. Gemma, N. Beatriz, B. De Josep, M. Cristina, Á. Marc, P. Luis, B. Ángel, C. Inés, G. Mikel, L. Carlos, P. María, d.M.R. Elisabeth, H. Jose, M.E.N. Jose, L.E. Artemio, P. Rodrigo, J. Cristina, A. Laura, S. Nuria, A. Estefanía, R. Lucía, P.C. Joaquim, R. Ángel, S. Anna, G. Joan, S. Eduard, B.A. Josefina, A. Ramon, B. Ana, M.G. Fernando, C. Antonio, B. Eduardo, S. Fernando, G. Jaime, S. Akiko, O. Mercedes, L. Enrique, M. Jaime, C. Pilar, C. Miguel, M. José, A.G. Francisco, Q. Elisa, O. Juan, C. Jaime, S. Antoni, T. Eugenia, S. de Ma, L.C. Antoni, T. Juan, C. Vicent, H. Xavier, L. Rosa, M.X. Marta, P. Mercè, R. Anna, R. Elisenda, P. José, M.H. Miquel, A.G. Fernando, F.B. Josep, M.V. Antonio, S. Jorge, E. Montserrat, F. Maria, E. Josep, M.R. Carmen, P. Juan, B. Joan, V. Enrique, Q. David, N. Adolfo, P. Antonio, M. Lidia, A. Vicente, P. Virginia, P. Teresa, S. Dolors, G. Eva, R. Teresa, R. Maria, P. Ma, M.C. Marta, M. Lourdes, P. Daniel, M. Ángel, C. Clara, R.P. Ceres, F.R. Ma, M.C. Sabino, R. Luis, R. Javier, F. Jose, L.C. Luis, C. Susana, O. Federico, B. Elena, P. José, M.B. Gloria, C. Juan, J.S. Antonio, N. Naccarati, A. Pardini, B. Vodickova, L. Müller, H. Talseth Palmer, B.A. Stibbard, G. Peterlongo, P. Nici, C. Veneroni, S. Li, L. Casey, G. Tenesa, A. Farrington, S.M. Tomlinson, I. Moreno, V. van Wezel, T. Wijnen, J. Dunlop, M. Radice, P. Scott, R.J. Vodicka, P. Ruiz Ponte, C. Brenner, H. Buch, S. Völzke, H. Hampe, J. Schafmayer, C. Lindblom, A. 1007 610 Universidad de Zaragoza Departamento de Medicina, Psiquiatría y Dermatología Medicina 1000 020 Universidad de Zaragoza Departamento de Anatomía Patológica, Medicina Legal y Forense y Toxicología Anatomía Patológica 8, 9 (2013), e72091 [6 pp] PLoS One PLoS One 1932-6203 176603 http://zaguan.unizar.es/record/63303/files/texto_completo.pdf Versión publicada 129590 http://zaguan.unizar.es/record/63303/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:63303 articulos driver 2018-05-18-10:36:32 ARTICLE