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 Balaguer & 151 others Gonzalo 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

15 Citations (Scopus)

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

Fingerprint

DNA Mismatch Repair
Polymorphism
colorectal neoplasms
meta-analysis
single nucleotide polymorphism
Single Nucleotide Polymorphism
Meta-Analysis
Colorectal Neoplasms
Repair
genetic polymorphism
Nucleotides
penetrance
Twin Studies
Penetrance
Neoplasm Genes
Genome-Wide Association Study
Linkage Disequilibrium
Environmental Exposure
linkage disequilibrium
case-control studies

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., ... 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

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 journalArticle

Picelli, S, Lorenzo Bermejo, J, Chang-Claude, J, Hoffmeister, M, Fernández-Rozadilla, C, Carracedo, A, Castells, A, Castellví-Bel, S, Juan, DM, Raquel, M, Marisa, M, Francisco, C, Jose, D, Carolina, I, Guadalupe, L, Alberto, I, Antoni, C, Virgínia, P, Sergi, CB, Balaguer, F, Victoria, G, Teresa, O, María Dolores, G, Maria, P, Anna, S, Leticia, M, Miriam, C, Josep, MP, Ángel, L, Javier, A, Javier, O, Joaquin, C, Ma, SD, 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, DMR, Elisabeth, H, Jose, MEN, Jose, LE, Artemio, P, Rodrigo, J, Cristina, A, Laura, S, Nuria, A, Estefanía, R, Lucía, PC, Joaquim, R, Ángel, S, Anna, G, Joan, S, Eduard, BA, Josefina, A, Ramon, B, Ana, MG, Fernando, C, Antonio, B, Eduardo, S, Fernando, G, Jaime, S, Akiko, O, Mercedes, L, Enrique, M, Jaime, C, Pilar, C, Miguel, M, José, ÁG, Francisco, Q, Elisa, O, Juan, C, Jaime, S, Antoni, T, Eugenia, S, de Ma, LC, Antoni, T, Juan, C, Vicent, H, Xavier, L, Rosa, MX, Marta, P, Mercè, R, Anna, R, Elisenda, P, José, MH, Miquel, AG, Fernando, FB, Josep, MV, Antonio, S, Jorge, E, Montserrat, F, Maria, E, Josep, MR, 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, MC, Marta, M, Lourdes, P, Daniel, M, Ángel, C, Clara, RP, Ceres, FR, Ma, MC, Sabino, R, Luis, R, Javier, F, Jose, LC, Luis, C, Susana, O, Federico, B, Elena, P, José, MB, Gloria, C, Juan, JS, Antonio, N, Naccarati, A, Pardini, B, Vodickova, L, Müller, H, Talseth-Palmer, BA, Stibbard, G, Peterlongo, P, Nici, C, Veneroni, S, Li, L, Casey, G, Tenesa, A, Farrington, SM, Tomlinson, I, Moreno, V, van Wezel, T, Wijnen, J, Dunlop, M, Radice, P, Scott, RJ, Vodicka, P, Ruiz-Ponte, C, Brenner, H, Buch, S, Völzke, H, Hampe, J, Schafmayer, C & Lindblom, A 2013, 'Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility', PLoS One, vol. 8, no. 9, e72091. https://doi.org/10.1371/journal.pone.0072091
Picelli S, Lorenzo Bermejo J, Chang-Claude J, Hoffmeister M, Fernández-Rozadilla C, Carracedo A et al. Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility. PLoS One. 2013 Sep 6;8(9). e72091. https://doi.org/10.1371/journal.pone.0072091
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. / Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility. In: PLoS One. 2013 ; Vol. 8, No. 9.
@article{0c3fd78f1f1542a19e9d2c6055e30ff7,
title = "Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility",
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.",
author = "Simone Picelli and {Lorenzo Bermejo}, Justo and Jenny Chang-Claude and Michael Hoffmeister and Ceres Fern{\'a}ndez-Rozadilla and Angel Carracedo and Antoni Castells and Sergi Castellv{\'i}-Bel and Juan, {Diego Morillas} and Mu{\~n}oz Raquel and Manzano Marisa and Colina Francisco and D{\'i}az Jose and Ibarrola Carolina and L{\'o}pez Guadalupe and Ib{\'a}{\~n}ez Alberto and Castells Antoni and Pi{\~n}ol Virg{\'i}nia and Sergi, {Castellv{\'i} Bel} and Francesc Balaguer and Gonzalo Victoria and Oca{\~n}a Teresa and {Mar{\'i}a Dolores}, Gir{\'a}ldez and Pellis{\'e} Maria and Serradesanferm Anna and Moreira Leticia and Cuatrecasas Miriam and Josep, {M. Piqu{\'e}} and Lanas {\'A}ngel and Alcedo Javier and Ortego Javier and Cubiella Joaquin and Ma, {Soledad D{\'i}ez} and Salgado Mercedes and S{\'a}nchez Eloy and Vega Mariano and Andreu Montserrat and Abuli Anna and Bessa Xavier and Iglesias Mar and Seoane Agust{\'i}n and Bory Felipe and Navarro Gemma and Bellosillo Beatriz and {De Josep}, Madeu and {\'A}lvarez Cristina and Puigveh{\'i} Marc and Bujanda Luis and Cosme {\'A}ngel and Gil In{\'e}s and Larzabal Mikel and Placer Carlos and Mar{\'i}a, {Del Mar Ram{\'i}rez} and Hijona Elisabeth and Jose, {M. Enr{\'i}quez Navascu{\'e}s} and Jose, {L. Elosegui} and Pay{\'a} Artemio and Jover Rodrigo and Alenda Cristina and Sempere Laura and Acame Nuria and Rojas Estefan{\'i}a and Luc{\'i}a, {P{\'e}rez Carbonell} and Rigau Joaquim and Serrano {\'A}ngel and Gim{\'e}nez Anna and Sal{\'o} Joan and Eduard, {Batiste Alentorn} and Autonell Josefina and Barniol Ramon and Ana, {Mar{\'i}a Garc{\'i}a} and Carballo Fernando and Bienvenido Antonio and Sanz Eduardo and Gonz{\'a}lez Fernando and S{\'a}nchez Jaime and Ono Akiko and Latorre Mercedes and Medina Enrique and Cuquerella Jaime and Canelles Pilar and Martorell Miguel and Jos{\'e}, {{\'A}ngel Garc{\'i}a} and Quiles Francisco and Orti Elisa and Clofent Juan and Seoane Jaime and Tard{\'i}o Antoni and Sanchez Eugenia and {de Ma}, {Luisa Castro} and Tard{\'i}o Antoni and Clofent Juan and Hern{\'a}ndez Vicent and Llor Xavier and Rosa, {M. Xicola} and Pi{\~n}ol Marta and Rosinach Merc{\`e} and Roca Anna and Pons Elisenda and Jos{\'e}, {M. Hern{\'a}ndez} and Miquel, {A. Gassull} and Fernando, {Fern{\'a}ndez Ba{\~n}ares} and Josep, {M. Viver} and Salas Antonio and Espin{\'o}s Jorge and Forn{\'e} Montserrat and Esteve Maria and Josep, {M. Re{\~n}{\'e}} and Pi{\~n}ol Carmen and Buenestado Juan and Vi{\~n}as Joan and Quintero Enrique and Nicol{\'a}s David and Parra Adolfo and Mart{\'i}n Antonio and Arg{\"u}ello Lidia and Pons Vicente and Pertejo Virginia and Sala Teresa and Gonzalez Dolors and Roman Eva and Ramon Teresa and Poca Maria and Ma, {Mar Concepci{\'o}n} and Martin Marta and P{\'e}triz Lourdes and Martinez Daniel and Carracedo {\'A}ngel and Clara, {Ruiz Ponte} and Ceres, {Fern{\'a}ndez Rozadilla} and Ma, {Magdalena Castro} and Riestra Sabino and Rodrigo Luis and Fern{\'a}ndez Javier and Jose, {Luis Cabriada} and Carre{\~n}o Luis and Oqui{\~n}ena Susana and Bolado Federico and Pe{\~n}a Elena and Jos{\'e}, {Manuel Blas} and Ce{\~n}a Gloria and Juan, {Jos{\'e} Sebasti{\'a}n} and Naranjo Antonio and Alessio Naccarati and Barbara Pardini and Ludmila Vodickova and Heiko M{\"u}ller and Talseth-Palmer, {Bente A.} and Geoffrey Stibbard and Paolo Peterlongo and Carmela Nici and Silvia Veneroni and Li Li and Graham Casey and Albert Tenesa and Farrington, {Susan M.} and Ian Tomlinson and Victor Moreno and {van Wezel}, Tom and Juul Wijnen and Malcolm Dunlop and Paolo Radice and Scott, {Rodney J.} and Pavel Vodicka and Clara Ruiz-Ponte and Hermann Brenner and Stephan Buch and Henry V{\"o}lzke and Jochen Hampe and Clemens Schafmayer and Annika Lindblom",
year = "2013",
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language = "English",
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journal = "PLoS One",
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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.

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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 -