title: Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium.
  
  
  METHODS
  CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family.
  
  
  RESULTS
  None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, P-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, P-value = 0.09, log-additive 0, 1, 2 alleles).
  
  
  CONCLUSIONS
  ARL11, ADH1C, GALNTL2 and IL6 genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Abulí
authors.forename: Ceres
authors.initials: C
authors.lastname: Fernández-Rozadilla
authors.forename: Virginia
authors.initials: V
authors.lastname: Alonso-Espinaco
authors.forename: Jenifer
authors.initials: J
authors.lastname: Muñoz
authors.forename: Victoria
authors.initials: V
authors.lastname: Gonzalo
authors.forename: Xavier
authors.initials: X
authors.lastname: Bessa
authors.forename: Dolors
authors.initials: D
authors.lastname: González
authors.forename: Joan
authors.initials: J
authors.lastname: Clofent
authors.forename: Joaquin
authors.initials: J
authors.lastname: Cubiella
authors.forename: Juan D
authors.initials: JD
authors.lastname: Morillas
authors.forename: Joaquim
authors.initials: J
authors.lastname: Rigau
authors.forename: Mercedes
authors.initials: M
authors.lastname: Latorre
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Bañares
authors.forename: Elena
authors.initials: E
authors.lastname: Peña
authors.forename: Sabino
authors.initials: S
authors.lastname: Riestra
authors.forename: Artemio
authors.initials: A
authors.lastname: Payá
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jover
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Xicola
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.forename: Luis
authors.initials: L
authors.lastname: Carvajal-Carmona
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Villanueva
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piqué
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Montserrat
authors.initials: M
authors.lastname: Andreu
authors.forename: Clara
authors.initials: C
authors.lastname: Ruiz-Ponte
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
mesh_terms: D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D009077:Mucins / Q000235:genetics*; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013030:Spain / Q000453:epidemiology
chemical_list: D009077:Mucins; D017350:N-Acetylgalactosaminyltransferases