A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the m...

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Autores: Fernández-Rozadilla, Ceres, Cazier, Jean-Baptiste, Tomlinson, Ian P., Carvajal Carmona, Luis G., Palles, Claire, Lamas, María J., Baiget Bastús, Montserrat, López Fernández, Luis A., Brea Fernández, Alejandro, Abulí, Anna, Bujanda, Luis, Clofent, Juan, Gonzalez, Dolors, Xicola, Rosa, Andreu, Montserrat, Bessa i Caserras, Xavier, Jover, Rodrigo, Llor, Xavier, Moreno Aguado, Víctor, Castells Garangou, Antoni, Carracedo Álvarez, Ángel, Castellví Bel, Sergi, Ruiz-Ponte, Clara
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2013
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/69159
Acesso em linha:https://hdl.handle.net/2445/69159
Access Level:Acceso aberto
Palavra-chave:Càncer colorectal
Polimorfisme genètic
Estadístiques
Colorectal cancer
Genetic polymorphisms
Statistics
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spelling A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12Fernández-Rozadilla, CeresCazier, Jean-BaptisteTomlinson, Ian P.Carvajal Carmona, Luis G.Palles, ClaireLamas, María J.Baiget Bastús, MontserratLópez Fernández, Luis A.Brea Fernández, AlejandroAbulí, AnnaBujanda, LuisClofent, JuanGonzalez, DolorsXicola, RosaAndreu, MontserratBessa i Caserras, XavierJover, RodrigoLlor, XavierMoreno Aguado, VíctorCastells Garangou, AntoniCarracedo Álvarez, ÁngelCastellví Bel, SergiRuiz-Ponte, ClaraCàncer colorectalPolimorfisme genèticEstadístiquesColorectal cancerGenetic polymorphismsStatisticsBackground: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.BioMed Central2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/69159Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1186/1471-2164-14-55Bmc Genomics, 2013, vol. 14, num. 55, p. 1-11http://dx.doi.org/10.1186/1471-2164-14-55cc-by (c) Fernández-Rozadilla, Ceres et al., 2013http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/691592026-05-27T06:46:51Z
dc.title.none.fl_str_mv A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
title A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
spellingShingle A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
Fernández-Rozadilla, Ceres
Càncer colorectal
Polimorfisme genètic
Estadístiques
Colorectal cancer
Genetic polymorphisms
Statistics
title_short A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
title_full A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
title_fullStr A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
title_full_unstemmed A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
title_sort A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
dc.creator.none.fl_str_mv Fernández-Rozadilla, Ceres
Cazier, Jean-Baptiste
Tomlinson, Ian P.
Carvajal Carmona, Luis G.
Palles, Claire
Lamas, María J.
Baiget Bastús, Montserrat
López Fernández, Luis A.
Brea Fernández, Alejandro
Abulí, Anna
Bujanda, Luis
Clofent, Juan
Gonzalez, Dolors
Xicola, Rosa
Andreu, Montserrat
Bessa i Caserras, Xavier
Jover, Rodrigo
Llor, Xavier
Moreno Aguado, Víctor
Castells Garangou, Antoni
Carracedo Álvarez, Ángel
Castellví Bel, Sergi
Ruiz-Ponte, Clara
author Fernández-Rozadilla, Ceres
author_facet Fernández-Rozadilla, Ceres
Cazier, Jean-Baptiste
Tomlinson, Ian P.
Carvajal Carmona, Luis G.
Palles, Claire
Lamas, María J.
Baiget Bastús, Montserrat
López Fernández, Luis A.
Brea Fernández, Alejandro
Abulí, Anna
Bujanda, Luis
Clofent, Juan
Gonzalez, Dolors
Xicola, Rosa
Andreu, Montserrat
Bessa i Caserras, Xavier
Jover, Rodrigo
Llor, Xavier
Moreno Aguado, Víctor
Castells Garangou, Antoni
Carracedo Álvarez, Ángel
Castellví Bel, Sergi
Ruiz-Ponte, Clara
author_role author
author2 Cazier, Jean-Baptiste
Tomlinson, Ian P.
Carvajal Carmona, Luis G.
Palles, Claire
Lamas, María J.
Baiget Bastús, Montserrat
López Fernández, Luis A.
Brea Fernández, Alejandro
Abulí, Anna
Bujanda, Luis
Clofent, Juan
Gonzalez, Dolors
Xicola, Rosa
Andreu, Montserrat
Bessa i Caserras, Xavier
Jover, Rodrigo
Llor, Xavier
Moreno Aguado, Víctor
Castells Garangou, Antoni
Carracedo Álvarez, Ángel
Castellví Bel, Sergi
Ruiz-Ponte, Clara
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Polimorfisme genètic
Estadístiques
Colorectal cancer
Genetic polymorphisms
Statistics
topic Càncer colorectal
Polimorfisme genètic
Estadístiques
Colorectal cancer
Genetic polymorphisms
Statistics
description Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/69159
url https://hdl.handle.net/2445/69159
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1186/1471-2164-14-55
Bmc Genomics, 2013, vol. 14, num. 55, p. 1-11
http://dx.doi.org/10.1186/1471-2164-14-55
dc.rights.none.fl_str_mv cc-by (c) Fernández-Rozadilla, Ceres et al., 2013
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Fernández-Rozadilla, Ceres et al., 2013
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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