A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12.
BACKGROUND
Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin.


RESULTS
Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance.


CONCLUSIONS
We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.
Galician Public Fundation of Genomic Medicine (FPGMX)-Grupo de Medicina Xenómica-Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERer)-IDIS, Santiago de Compostela, 15706, Spain.
Ceres
C
Fernandez-Rozadilla
Jean-Baptiste
JB
Cazier
Ian P
IP
Tomlinson
Luis G
LG
Carvajal-Carmona
Claire
C
Palles
María J
MJ
Lamas
Montserrat
M
Baiget
Luis A
LA
López-Fernández
Alejandro
A
Brea-Fernández
Anna
A
Abulí
Luis
L
Bujanda
Juan
J
Clofent
Dolors
D
Gonzalez
Rosa
R
Xicola
Montserrat
M
Andreu
Xavier
X
Bessa
Rodrigo
R
Jover
Xavier
X
Llor
Víctor
V
Moreno
Antoni
A
Castells
Ángel
Á
Carracedo
Sergi
S
Castellvi-Bel
Clara
C
Ruiz-Ponte
D000368:Aged; D000369:Aged, 80 and over; D002878:Chromosomes, Human, Pair 1; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012307:Risk Factors; D013030:Spain; D044465:White People / Q000235:genetics*
D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases