A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-01-26

AUTHORS

Ceres Fernandez-Rozadilla, Jean-Baptiste Cazier, Ian P Tomlinson, Luis G Carvajal-Carmona, Claire Palles, María J Lamas, Montserrat Baiget, Luis A López-Fernández, Alejandro Brea-Fernández, Anna Abulí, Luis Bujanda, Juan Clofent, Dolors Gonzalez, Rosa Xicola, Montserrat Andreu, Xavier Bessa, Rodrigo Jover, Xavier Llor, Víctor Moreno, Antoni Castells, Ángel Carracedo, Sergi Castellvi-Bel, Clara Ruiz-Ponte

ABSTRACT

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. More... »

PAGES

55-55

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  • Journal

    TITLE

    BMC Genomics

    ISSUE

    1

    VOLUME

    14

    Author Affiliations

  • Galician Public Fundation of Genomic Medicine (FPGMX)-Grupo de Medicina Xenómica-Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERer)-IDIS, Santiago de Compostela, 15706, Spain
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
  • NIHR Comprehensive Biomedical Research Centre, University of Oxford, Oxford, OX3 7BN, UK
  • Department of Biochemistry and Molecular Medicine School of Medicine University of California, Davis, California, USA
  • Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Santiago de Compostela, 15706, Spain
  • Genetics Department, Hospital de Santa Creu I Sant Pau, Barcelona, 08025, Spain
  • Pharmacogenetics & Pharmacogenomics Laboratory, Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, 28007, Spain
  • Department of Gastroenterology, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, 08036, Spain
  • Gastroenterology Department, Donostia Hospital, CIBERehd, University of the Basque Country, San Sebastián, 20014, Spain
  • Section of Digestive Diseases, Internal Medicine Department, Hospital Sagunto, Valencia, 46520, Spain
  • Servicio de Patologia Digestiva, Hospital Sant PAu, Barcelona, 08003, Spain
  • Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, IL, 60607, USA
  • Gastroenterology Department, Hospital del Mar, Barcelona, 08003, Spain
  • Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, 03010, Spain
  • Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Centre (IDIBELL), CIBERESP, Barcelona, 08907, Spain
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1471-2164-14-55

    DOI

    http://dx.doi.org/10.1186/1471-2164-14-55

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032093752

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23350875


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