Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility

Simone Picelli, Justo Lorenzo Bermejo, Jenny Chang-Claude, Michael Hoffmeister, Ceres Fernández-Rozadilla, Angel Carracedo, Antoni Castells, Sergi Castellví-Bel, Diego Morillas Juan, Muñoz Raquel, Manzano Marisa, Colina Francisco, Díaz Jose, Ibarrola Carolina, López Guadalupe, Ibáñez Alberto, Castells Antoni, Piñol Virgínia, Castellví Bel Sergi, Francesc BalaguerGonzalo Victoria, Ocaña Teresa, Giráldez María Dolores, Pellisé Maria, Serradesanferm Anna, Moreira Leticia, Cuatrecasas Miriam, M. Piqué Josep, Lanas Ángel, Alcedo Javier, Ortego Javier, Cubiella Joaquin, Soledad Díez Ma, Salgado Mercedes, Sánchez Eloy, Vega Mariano, Andreu Montserrat, Abuli Anna, Bessa Xavier, Iglesias Mar, Seoane Agustín, Bory Felipe, Navarro Gemma, Bellosillo Beatriz, Madeu De Josep, Álvarez Cristina, Puigvehí Marc, Bujanda Luis, Cosme Ángel, Gil Inés, Larzabal Mikel, Placer Carlos, Del Mar Ramírez María, Hijona Elisabeth, M. Enríquez Navascués Jose, L. Elosegui Jose, Payá Artemio, Jover Rodrigo, Alenda Cristina, Sempere Laura, Acame Nuria, Rojas Estefanía, Pérez Carbonell Lucía, Rigau Joaquim, Serrano Ángel, Giménez Anna, Saló Joan, Batiste Alentorn Eduard, Autonell Josefina, Barniol Ramon, María García Ana, Carballo Fernando, Bienvenido Antonio, Sanz Eduardo, González Fernando, Sánchez Jaime, Ono Akiko, Latorre Mercedes, Medina Enrique, Cuquerella Jaime, Canelles Pilar, Martorell Miguel, Ángel García José, Quiles Francisco, Orti Elisa, Clofent Juan, Seoane Jaime, Tardío Antoni, Sanchez Eugenia, Luisa Castro de Ma, Tardío Antoni, Clofent Juan, Hernández Vicent, Llor Xavier, M. Xicola Rosa, Piñol Marta, Rosinach Mercè, Roca Anna, Pons Elisenda, M. Hernández José, A. Gassull Miquel, Fernández Bañares Fernando, M. Viver Josep, Salas Antonio, Espinós Jorge, Forné Montserrat, Esteve Maria, M. Reñé Josep, Piñol Carmen, Buenestado Juan, Viñas Joan, Quintero Enrique, Nicolás David, Parra Adolfo, Martín Antonio, Argüello Lidia, Pons Vicente, Pertejo Virginia, Sala Teresa, Gonzalez Dolors, Roman Eva, Ramon Teresa, Poca Maria, Mar Concepción Ma, Martin Marta, Pétriz Lourdes, Martinez Daniel, Carracedo Ángel, Ruiz Ponte Clara, Fernández Rozadilla Ceres, Magdalena Castro Ma, Riestra Sabino, Rodrigo Luis, Fernández Javier, Luis Cabriada Jose, Carreño Luis, Oquiñena Susana, Bolado Federico, Peña Elena, Manuel Blas José, Ceña Gloria, José Sebastián Juan, Naranjo Antonio, Alessio Naccarati, Barbara Pardini, Ludmila Vodickova, Heiko Müller, Bente A. Talseth-Palmer, Geoffrey Stibbard, Paolo Peterlongo, Carmela Nici, Silvia Veneroni, Li Li, Graham Casey, Albert Tenesa, Susan M. Farrington, Ian Tomlinson, Victor Moreno, Tom van Wezel, Juul Wijnen, Malcolm Dunlop, Paolo Radice, Rodney J. Scott, Pavel Vodicka, Clara Ruiz-Ponte, Hermann Brenner, Stephan Buch, Henry Völzke, Jochen Hampe, Clemens Schafmayer, Annika Lindblom

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere72091
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 6 2013

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Picelli, S., 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., ... Lindblom, A. (2013). Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility. PLoS One, 8(9), [e72091]. https://doi.org/10.1371/journal.pone.0072091