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-Rozadilla, Jean Baptiste Cazier, Ian P. Tomlinson, Luis 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 CastellsÁngel Carracedo, Sergi Castellvi-Bel, Clara Ruiz-Ponte

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Article number55
JournalBMC Genomics
Volume14
Issue number1
DOIs
StatePublished - Jan 26 2013

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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    Fernandez-Rozadilla, C., Cazier, J. B., Tomlinson, I. P., Carvajal-Carmona, L., Palles, C., Lamas, M. J., Baiget, M., López-Fernández, L. A., Brea-Fernández, A., Abulí, A., Bujanda, L., Clofent, J., Gonzalez, D., Xicola, R., Andreu, M., Bessa, X., Jover, R., Llor, X., Moreno, V., ... Ruiz-Ponte, C. (2013). A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12. BMC Genomics, 14(1), [55]. https://doi.org/10.1186/1471-2164-14-55