Susceptibility genetic variants associated with colorectal cancer risk correlate with cancer phenotype.
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.
Abulí
Anna
A
Department of Gastroenterology, Hospital del Mar, Institut Municipal d'Investigació Mèdica, Pompeu Fabra University, Barcelona, Catalonia, Spain.
Bessa
Xavier
X
González
Juan Ramón
JR
Ruiz-Ponte
Clara
C
Cáceres
Alejandro
A
Muñoz
Jenifer
J
Gonzalo
Victoria
V
Balaguer
Francesc
F
Fernández-Rozadilla
Ceres
C
González
Dolors
D
de Castro
Luisa
L
Clofent
Juan
J
Bujanda
Luís
L
Cubiella
Joaquín
J
Reñé
Josep M A
JM
Morillas
Juan Diego
JD
Lanas
Angel
A
Rigau
Joaquim
J
García
Ana M A
AM
Latorre
Mercedes
M
Saló
Joan
J
Fernández Bañares
Fernando
F
Argüello
Lídia
L
Peña
Elena
E
Vilella
Angels
A
Riestra
Sabino
S
Carreño
Ramiro
R
Paya
Artemio
A
Alenda
Cristina
C
Xicola
Rosa M
RM
Doyle
Brian J
BJ
Jover
Rodrigo
R
Llor
Xavier
X
Carracedo
Angel
A
Castells
Antoni
A
Castellví-Bel
Sergi
S
Andreu
Montserrat
M
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