title: A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis.
abstract: BACKGROUND
  Non-hereditary colorectal cancer (CRC) is a complex disorder resulting from the combination of genetic and non-genetic factors. Genome-wide association studies (GWAS) are useful for identifying such genetic susceptibility factors. However, the single loci so far associated with CRC only represent a fraction of the genetic risk for CRC development in the general population. Therefore, many other genetic risk variants alone and in combination must still remain to be discovered. The aim of this work was to search for genetic risk factors for CRC, by performing single-locus and two-locus GWAS in the Spanish population.
  
  
  RESULTS
  A total of 801 controls and 500 CRC cases were included in the discovery GWAS dataset. 77 single nucleotide polymorphisms (SNP)s from single-locus and 243 SNPs from two-locus association analyses were selected for replication in 423 additional CRC cases and 1382 controls. In the meta-analysis, one SNP, rs3987 at 4q26, reached GWAS significant p-value (p = 4.02×10(-8)), and one SNP pair, rs1100508 CG and rs8111948 AA, showed a trend for two-locus association (p = 4.35×10(-11)). Additionally, our GWAS confirmed the previously reported association with CRC of five SNPs located at 3q36.2 (rs10936599), 8q24 (rs10505477), 8q24.21(rs6983267), 11q13.4 (rs3824999) and 14q22.2 (rs4444235).
  
  
  CONCLUSIONS
  Our GWAS for CRC patients from Spain confirmed some previously reported associations for CRC and yielded a novel candidate risk SNP, located at 4q26. Epistasis analyses also yielded several novel candidate susceptibility pairs that need to be validated in independent analyses.
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Infectious Diseases and Microbiology Unit, Hospital Nuestra Señora de Valme, Seville, Spain; Institute of Biomedicine of Seville (IBIS), Seville, Spain.
authors: Luis M
authors: LM
authors: Real
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain.
authors: Agustín
authors: A
authors: Ruiz
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Bioinfosol, Seville, Spain.
authors: Javier
authors: J
authors: Gayán
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Andalusian Center for Bioinformatic Studies (CAEBI), Seville, Spain.
authors: Antonio
authors: A
authors: González-Pérez
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Andalusian Center for Bioinformatic Studies (CAEBI), Seville, Spain.
authors: María E
authors: ME
authors: Sáez
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Institute of Biomedicine of Seville (IBIS), Seville, Spain.
authors: Reposo
authors: R
authors: Ramírez-Lorca
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Institute of Biomedicine of Seville (IBIS), Seville, Spain.
authors: Francisco J
authors: FJ
authors: Morón
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Barcelona, Spain.
authors: Juan
authors: J
authors: Velasco
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Department of Pathology, Hospital Universitario Germans Trias i Pujol (HUGTP), Badalona, Barcelona, Spain.
authors: Ruth
authors: R
authors: Marginet-Flinch
authors: Department of Pathology, Hospital Universitario Germans Trias i Pujol (HUGTP), Badalona, Barcelona, Spain.
authors: Eva
authors: E
authors: Musulén
authors: Department of Structural Genomics, Neocodex, Seville, Spain.
authors: José M
authors: JM
authors: Carrasco
authors: Department of Structural Genomics, Neocodex, Seville, Spain; Department of Oncology, Hospital Virgen del Rocío, Seville, Spain.
authors: Concha
authors: C
authors: Moreno-Rey
authors: Department of Structural Genomics, Neocodex, Seville, Spain.
authors: Enrique
authors: E
authors: Vázquez
authors: Department of Oncology, Hospital Virgen del Rocío, Seville, Spain.
authors: Manuel
authors: M
authors: Chaves-Conde
authors: Department of Oncology, Hospital Virgen del Rocío, Seville, Spain.
authors: Jose A
authors: JA
authors: Moreno-Nogueira
authors: Colorectal Surgery Unit, Hospital 12 de Octubre, Madrid, Spain.
authors: Manuel
authors: M
authors: Hidalgo-Pascual
authors: Colorectal Surgery Unit, Hospital 12 de Octubre, Madrid, Spain.
authors: Eduardo
authors: E
authors: Ferrero-Herrero
authors: Department of Gastroenterology, Hospital Clínic, University of Barcelona, CIBEREHD, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Sergi
authors: S
authors: Castellví-Bel
authors: Department of Gastroenterology, Hospital Clínic, University of Barcelona, CIBEREHD, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Antoni
authors: A
authors: Castells
authors: Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Red de Enfermedades Raras, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, A Coruña, Spain.
authors: Ceres
authors: C
authors: Fernandez-Rozadilla
authors: Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Red de Enfermedades Raras, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, A Coruña, Spain.
authors: Clara
authors: C
authors: Ruiz-Ponte
authors: Galician Public Foundation of Genomic Medicine, Centro de Investigación Biomédica en Red de Enfermedades Raras, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, A Coruña, Spain.
authors: Angel
authors: A
authors: Carracedo
authors: Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Barcelona, Spain.
authors: Beatriz
authors: B
authors: González
authors: Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Barcelona, Spain.
authors: Sergio
authors: S
authors: Alonso
authors: Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Barcelona, Spain; Sanford-Burnham Medical Research Institute (SBMRI), La Jolla, California United States of America; Instituciò Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors: Manuel
authors: M
authors: Perucho
mesh_terms: D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D013030:Spain