title: Susceptibility genetic variants associated with colorectal cancer risk correlate with cancer phenotype.
abstract: OBJECTIVE
  Ten common low-penetrant genetic variants have been consistently associated with colorectal cancer (CRC) risk; little is known about the correlation between these variants and CRC phenotype. Characterization of such a correlation would improve CRC management and prevention programs. We assessed the association between these genetic variants and CRC phenotype in patients and modeled pairwise combinations to detect epistasis.
  
  
  METHODS
  The validation population corresponded to a prospective, multicenter, population-based cohort (EPICOLON I) of 1096 patients with newly diagnosed CRC. The replication set was an independent, prospective, multicenter Spanish cohort (EPICOLON II) of 895 patients with newly diagnosed CRC. For individual single nucleotide polymorphism (SNP) association analyses, a multivariate method using logistic regression was applied in EPICOLON I and subsequently prospectively validated in EPICOLON II. Interactions between SNPs were assessed using the likelihood ratio test.
  
  
  RESULTS
  Validated results confirmed that the C allele on 8q23.3 (rs16892766) was significantly associated with advanced-stage tumors (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.15-1.90; P value = 4.9 x 10(-3)). The G allele on 8q24.21 (rs6983267) was more common in patients with a familial history of CRC (OR, 2.02; 95% CI, 1.35-3.03; P value = 3.9 x 10(-4)). The combination of rs6983267 on 8q24.21 and rs9929218 on 16q22.2 was associated with a history of colorectal adenoma (carriers of GG and AA, respectively; OR, 2.28; 95% CI, 1.32-3.93; P = 5.0 x 10(-4)).
  
  
  CONCLUSIONS
  CRC susceptibility variants at 8q23.3, 8q24.21, and 16q22.2 appear to be associated with cancer phenotype. These findings might be used to develop screening and surveillance strategies.
authors.affiliation: Department of Gastroenterology, Hospital del Mar, Institut Municipal d'Investigació Mèdica, Pompeu Fabra University, Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Abulí
authors.forename: Xavier
authors.initials: X
authors.lastname: Bessa
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: González
authors.forename: Clara
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authors.lastname: Ruiz-Ponte
authors.forename: Alejandro
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authors.lastname: Cáceres
authors.forename: Jenifer
authors.initials: J
authors.lastname: Muñoz
authors.forename: Victoria
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authors.lastname: Gonzalo
authors.forename: Francesc
authors.initials: F
authors.lastname: Balaguer
authors.forename: Ceres
authors.initials: C
authors.lastname: Fernández-Rozadilla
authors.forename: Dolors
authors.initials: D
authors.lastname: González
authors.forename: Luisa
authors.initials: L
authors.lastname: de Castro
authors.forename: Juan
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authors.lastname: Clofent
authors.forename: Luís
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authors.lastname: Bujanda
authors.forename: Joaquín
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authors.lastname: Cubiella
authors.forename: Josep M A
authors.initials: JM
authors.lastname: Reñé
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Morillas
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.forename: Joaquim
authors.initials: J
authors.lastname: Rigau
authors.forename: Ana M A
authors.initials: AM
authors.lastname: García
authors.forename: Mercedes
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authors.lastname: Latorre
authors.forename: Joan
authors.initials: J
authors.lastname: Saló
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández Bañares
authors.forename: Lídia
authors.initials: L
authors.lastname: Argüello
authors.forename: Elena
authors.initials: E
authors.lastname: Peña
authors.forename: Angels
authors.initials: A
authors.lastname: Vilella
authors.forename: Sabino
authors.initials: S
authors.lastname: Riestra
authors.forename: Ramiro
authors.initials: R
authors.lastname: Carreño
authors.forename: Artemio
authors.initials: A
authors.lastname: Paya
authors.forename: Cristina
authors.initials: C
authors.lastname: Alenda
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Xicola
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Doyle
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jover
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
authors.forename: Montserrat
authors.initials: M
authors.lastname: Andreu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002885:Chromosomes, Human, Pair 16; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain