Single nucleotide polymorphisms in the Wnt and BMP pathways and colorectal cancer risk in a Spanish cohort.
BACKGROUND
Colorectal cancer (CRC) is considered a complex disease, and thus the majority of the genetic susceptibility is thought to lie in the form of low-penetrance variants following a polygenic model of inheritance. Candidate-gene studies have so far been one of the basic approaches taken to identify these susceptibility variants. The consistent involvement of some signaling routes in carcinogenesis provided support for pathway-based studies as a natural strategy to select genes that could potentially harbour new susceptibility loci.


RESULTS
We selected two main carcinogenesis-related pathways: Wnt and BMP, in order to screen the implicated genes for new risk variants. We then conducted a case-control association study in 933 CRC cases and 969 controls based on coding and regulatory SNPs. We also included rs4444235 and rs9929218, which did not fulfill our selection criteria but belonged to two genes in the BMP pathway and had consistently been linked to CRC in previous studies. Neither allelic, nor genotypic or haplotypic analyses showed any signs of association between the 37 screened variants and CRC risk. Adjustments for sex and age, and stratified analysis between sporadic and control groups did not yield any positive results either.


CONCLUSIONS
Despite the relevance of both pathways in the pathogenesis of the disease, and the fact that this is indeed the first study that considers these pathways as a candidate-gene selection approach, our study does not present any evidence of the presence of low-penetrance variants for the selected markers in any of the considered genes in our cohort.
Fernández-Rozadilla
Ceres
C
Galician Public Foundation of Genomic Medicine (FPGMX), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain.
de Castro
Luisa
L
Clofent
Juan
J
Brea-Fernández
Alejandro
A
Bessa
Xavier
X
Abulí
Anna
A
Andreu
Montserrat
M
Jover
Rodrigo
R
Xicola
Rosa
R
Llor
Xavier
X
Castells
Antoni
A
Castellví-Bel
Sergi
S
Carracedo
Angel
A
Ruiz-Ponte
Clara
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D015398:Signal Transduction; D013030:Spain / Q000453:epidemiology; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D051153:Wnt Proteins