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

Ceres Fernandez-Rozadilla1, Jean-Baptiste Cazier2, Ian P Tomlinson23, Luis G Carvajal-Carmona4, Claire Palles2, María J Lamas5, Montserrat Baiget6, Luis A López-Fernández7, Alejandro Brea-Fernández1, Anna Abulí89, Luis Bujanda10, Juan Clofent1112, Dolors Gonzalez13, Rosa Xicola14, Montserrat Andreu8, Xavier Bessa8, Rodrigo Jover15, Xavier Llor14, The EPICOLON Consortium, Víctor Moreno16, Antoni Castells9, Ángel Carracedo1, Sergi Castellvi-Bel9 and Clara Ruiz-Ponte1*

Author affiliations

1 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

2 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK

3 NIHR Comprehensive Biomedical Research Centre, University of Oxford, Oxford, OX3 7BN, UK

4 Department of Biochemistry and Molecular Medicine School of Medicine University of California, Davis, California, USA

5 Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Santiago de Compostela, 15706, Spain

6 Genetics Department, Hospital de Santa Creu I Sant Pau, Barcelona, 08025, Spain

7 Pharmacogenetics & Pharmacogenomics Laboratory, Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón,, Madrid, 28007, Spain

8 Gastroenterology Department, Hospital del Mar, Barcelona, 08003, Spain

9 Department of Gastroenterology, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, 08036, Spain

10 Gastroenterology Department, Donostia Hospital, CIBERehd, University of the Basque Country, San Sebastián, 20014, Spain

11 Gastroenterology Department, Hospital do Meixoeiro, Vigo, 36214, Spain

12 Section of Digestive Diseases, Internal Medicine Department, Hospital Sagunto, Valencia, 46520, Spain

13 Servicio de Patologia Digestiva, Hospital Sant PAu, Barcelona, 08003, Spain

14 Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, IL, 60607, USA

15 Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, 03010, Spain

16 Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Centre (IDIBELL), CIBERESP, Barcelona, 08907, Spain

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Citation and License

BMC Genomics 2013, 14:55  doi:10.1186/1471-2164-14-55

Published: 26 January 2013



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.


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.


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.

GWAS; SNPs; Colorectal cancer; Spanish cohort; 1p33; 8p12