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

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. ; Balaguer, F. ; Victoria, G. ; Teresa, O. ; María Dolores, G. ; Maria, P. ; Anna, S. ; Leticia, M. ; Miriam, C. ; Josep, M.P. ; Lanas, A. (Universidad de Zaragoza) ; Alcedo, J. ; 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.

Resumen: 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.

Idioma: Inglés

DOI: 10.1371/journal.pone.0072091

Año: 2013

Publicado en: PLoS One 8, 9 (2013), e72091 [6 pp]
ISSN: 1932-6203

Factor impacto JCR: 3.534 (2013)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 8 / 56 = 0.143 (2013) - Q1 - T1

Financiación: info:eu-repo/grantAgreement/ES/FIS/CP-03-0070
Financiación: info:eu-repo/grantAgreement/ES/FIS FEDER/PS09-02368
Financiación: info:eu-repo/grantAgreement/ES/FIS FEDER/08-0024
Financiación: info:eu-repo/grantAgreement/ES/FIS FEDER/08-1276
Financiación: info:eu-repo/grantAgreement/ES/FIS FEDER/11-00219
Financiación: info:eu-repo/grantAgreement/ES/FIS FEDER/11-00681
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI08-1635
Financiación: info:eu-repo/grantAgreement/ES/FIS/PS09-1037
Financiación: info:eu-repo/grantAgreement/ES/MICINN/SAF2010-19273

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Medicina (Departamento de Medicina, Psiquiatría y Dermatología)
Área (Departamento): Anatomía Patológica (Departamento de Anatomía Patológica, Medicina Legal y Forense y Toxicología)