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 language | English |
|---|---|
| Article number | e72091 |
| Journal | PLoS One |
| Volume | 8 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 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
Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility. / Picelli, Simone; Lorenzo Bermejo, Justo; Chang-Claude, Jenny; Hoffmeister, Michael; Fernández-Rozadilla, Ceres; Carracedo, Angel; Castells, Antoni; Castellví-Bel, Sergi; Juan, Diego Morillas; Raquel, Muñoz; Marisa, Manzano; Francisco, Colina; Jose, Díaz; Carolina, Ibarrola; Guadalupe, López; Alberto, Ibáñez; Antoni, Castells; Virgínia, Piñol; Sergi, Castellví Bel; Balaguer, Francesc; Victoria, Gonzalo; Teresa, Ocaña; María Dolores, Giráldez; Maria, Pellisé; Anna, Serradesanferm; Leticia, Moreira; Miriam, Cuatrecasas; Josep, M. Piqué; Ángel, Lanas; Javier, Alcedo; Javier, Ortego; Joaquin, Cubiella; Ma, Soledad Díez; Mercedes, Salgado; Eloy, Sánchez; Mariano, Vega; Montserrat, Andreu; Anna, Abuli; Xavier, Bessa; Mar, Iglesias; Agustín, Seoane; Felipe, Bory; Gemma, Navarro; Beatriz, Bellosillo; De Josep, Madeu; Cristina, Álvarez; Marc, Puigvehí; Luis, Bujanda; Ángel, Cosme; Inés, Gil; Mikel, Larzabal; Carlos, Placer; María, Del Mar Ramírez; Elisabeth, Hijona; Jose, M. Enríquez Navascués; Jose, L. Elosegui; Artemio, Payá; Rodrigo, Jover; Cristina, Alenda; Laura, Sempere; Nuria, Acame; Estefanía, Rojas; Lucía, Pérez Carbonell; Joaquim, Rigau; Ángel, Serrano; Anna, Giménez; Joan, Saló; Eduard, Batiste Alentorn; Josefina, Autonell; Ramon, Barniol; Ana, María García; Fernando, Carballo; Antonio, Bienvenido; Eduardo, Sanz; Fernando, González; Jaime, Sánchez; Akiko, Ono; Mercedes, Latorre; Enrique, Medina; Jaime, Cuquerella; Pilar, Canelles; Miguel, Martorell; José, Ángel García; Francisco, Quiles; Elisa, Orti; Juan, Clofent; Jaime, Seoane; Antoni, Tardío; Eugenia, Sanchez; de Ma, Luisa Castro; Antoni, Tardío; Juan, Clofent; Vicent, Hernández; Xavier, Llor; Rosa, M. Xicola; Marta, Piñol; Mercè, Rosinach; Anna, Roca; Elisenda, Pons; José, M. Hernández; Miquel, A. Gassull; Fernando, Fernández Bañares; Josep, M. Viver; Antonio, Salas; Jorge, Espinós; Montserrat, Forné; Maria, Esteve; Josep, M. Reñé; Carmen, Piñol; Juan, Buenestado; Joan, Viñas; Enrique, Quintero; David, Nicolás; Adolfo, Parra; Antonio, Martín; Lidia, Argüello; Vicente, Pons; Virginia, Pertejo; Teresa, Sala; Dolors, Gonzalez; Eva, Roman; Teresa, Ramon; Maria, Poca; Ma, Mar Concepción; Marta, Martin; Lourdes, Pétriz; Daniel, Martinez; Ángel, Carracedo; Clara, Ruiz Ponte; Ceres, Fernández Rozadilla; Ma, Magdalena Castro; Sabino, Riestra; Luis, Rodrigo; Javier, Fernández; Jose, Luis Cabriada; Luis, Carreño; Susana, Oquiñena; Federico, Bolado; Elena, Peña; José, Manuel Blas; Gloria, Ceña; Juan, José Sebastián; Antonio, Naranjo; 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, Victor; 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: PLoS One, Vol. 8, No. 9, e72091, 06.09.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility
AU - Picelli, Simone
AU - Lorenzo Bermejo, Justo
AU - Chang-Claude, Jenny
AU - Hoffmeister, Michael
AU - Fernández-Rozadilla, Ceres
AU - Carracedo, Angel
AU - Castells, Antoni
AU - Castellví-Bel, Sergi
AU - Juan, Diego Morillas
AU - Raquel, Muñoz
AU - Marisa, Manzano
AU - Francisco, Colina
AU - Jose, Díaz
AU - Carolina, Ibarrola
AU - Guadalupe, López
AU - Alberto, Ibáñez
AU - Antoni, Castells
AU - Virgínia, Piñol
AU - Sergi, Castellví Bel
AU - Balaguer, Francesc
AU - Victoria, Gonzalo
AU - Teresa, Ocaña
AU - María Dolores, Giráldez
AU - Maria, Pellisé
AU - Anna, Serradesanferm
AU - Leticia, Moreira
AU - Miriam, Cuatrecasas
AU - Josep, M. Piqué
AU - Ángel, Lanas
AU - Javier, Alcedo
AU - Javier, Ortego
AU - Joaquin, Cubiella
AU - Ma, Soledad Díez
AU - Mercedes, Salgado
AU - Eloy, Sánchez
AU - Mariano, Vega
AU - Montserrat, Andreu
AU - Anna, Abuli
AU - Xavier, Bessa
AU - Mar, Iglesias
AU - Agustín, Seoane
AU - Felipe, Bory
AU - Gemma, Navarro
AU - Beatriz, Bellosillo
AU - De Josep, Madeu
AU - Cristina, Álvarez
AU - Marc, Puigvehí
AU - Luis, Bujanda
AU - Ángel, Cosme
AU - Inés, Gil
AU - Mikel, Larzabal
AU - Carlos, Placer
AU - María, Del Mar Ramírez
AU - Elisabeth, Hijona
AU - Jose, M. Enríquez Navascués
AU - Jose, L. Elosegui
AU - Artemio, Payá
AU - Rodrigo, Jover
AU - Cristina, Alenda
AU - Laura, Sempere
AU - Nuria, Acame
AU - Estefanía, Rojas
AU - Lucía, Pérez Carbonell
AU - Joaquim, Rigau
AU - Ángel, Serrano
AU - Anna, Giménez
AU - Joan, Saló
AU - Eduard, Batiste Alentorn
AU - Josefina, Autonell
AU - Ramon, Barniol
AU - Ana, María García
AU - Fernando, Carballo
AU - Antonio, Bienvenido
AU - Eduardo, Sanz
AU - Fernando, González
AU - Jaime, Sánchez
AU - Akiko, Ono
AU - Mercedes, Latorre
AU - Enrique, Medina
AU - Jaime, Cuquerella
AU - Pilar, Canelles
AU - Miguel, Martorell
AU - José, Ángel García
AU - Francisco, Quiles
AU - Elisa, Orti
AU - Juan, Clofent
AU - Jaime, Seoane
AU - Antoni, Tardío
AU - Eugenia, Sanchez
AU - de Ma, Luisa Castro
AU - Antoni, Tardío
AU - Juan, Clofent
AU - Vicent, Hernández
AU - Xavier, Llor
AU - Rosa, M. Xicola
AU - Marta, Piñol
AU - Mercè, Rosinach
AU - Anna, Roca
AU - Elisenda, Pons
AU - José, M. Hernández
AU - Miquel, A. Gassull
AU - Fernando, Fernández Bañares
AU - Josep, M. Viver
AU - Antonio, Salas
AU - Jorge, Espinós
AU - Montserrat, Forné
AU - Maria, Esteve
AU - Josep, M. Reñé
AU - Carmen, Piñol
AU - Juan, Buenestado
AU - Joan, Viñas
AU - Enrique, Quintero
AU - David, Nicolás
AU - Adolfo, Parra
AU - Antonio, Martín
AU - Lidia, Argüello
AU - Vicente, Pons
AU - Virginia, Pertejo
AU - Teresa, Sala
AU - Dolors, Gonzalez
AU - Eva, Roman
AU - Teresa, Ramon
AU - Maria, Poca
AU - Ma, Mar Concepción
AU - Marta, Martin
AU - Lourdes, Pétriz
AU - Daniel, Martinez
AU - Ángel, Carracedo
AU - Clara, Ruiz Ponte
AU - Ceres, Fernández Rozadilla
AU - Ma, Magdalena Castro
AU - Sabino, Riestra
AU - Luis, Rodrigo
AU - Javier, Fernández
AU - Jose, Luis Cabriada
AU - Luis, Carreño
AU - Susana, Oquiñena
AU - Federico, Bolado
AU - Elena, Peña
AU - José, Manuel Blas
AU - Gloria, Ceña
AU - Juan, José Sebastián
AU - Antonio, Naranjo
AU - Naccarati, Alessio
AU - Pardini, Barbara
AU - Vodickova, Ludmila
AU - Müller, Heiko
AU - Talseth-Palmer, Bente A.
AU - Stibbard, Geoffrey
AU - Peterlongo, Paolo
AU - Nici, Carmela
AU - Veneroni, Silvia
AU - Li, Li
AU - Casey, Graham
AU - Tenesa, Albert
AU - Farrington, Susan M.
AU - Tomlinson, Ian
AU - Moreno, Victor
AU - van Wezel, Tom
AU - Wijnen, Juul
AU - Dunlop, Malcolm
AU - Radice, Paolo
AU - Scott, Rodney J.
AU - Vodicka, Pavel
AU - Ruiz-Ponte, Clara
AU - Brenner, Hermann
AU - Buch, Stephan
AU - Völzke, Henry
AU - Hampe, Jochen
AU - Schafmayer, Clemens
AU - Lindblom, Annika
PY - 2013/9/6
Y1 - 2013/9/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84883635842&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883635842&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0072091
DO - 10.1371/journal.pone.0072091
M3 - Article
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 9
M1 - e72091
ER -