TY - JOUR
T1 - A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
AU - Fernandez-Rozadilla, Ceres
AU - Cazier, Jean-Baptiste
AU - Tomlinson, Ian P
AU - Carvajal-Carmona, Luis G
AU - Palles, Claire
AU - Lamas, María J
AU - Baiget, Montserrat
AU - López-Fernández, Luis A
AU - Brea-Fernández, Alejandro
AU - Abulí, Anna
AU - Bujanda, Luis
AU - Clofent, Juan
AU - Gonzalez, Dolors
AU - Xicola, Rosa
AU - Andreu, Montserrat
AU - Bessa, Xavier
AU - Jover, Rodrigo
AU - Llor, Xavier
AU - Moreno, Víctor
AU - Castells, Antoni
AU - Carracedo, Ángel
AU - Castellvi-Bel, Sergi
AU - Ruiz-Ponte, Clara
AU - EPICOLON Consortium
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Chromosomes, Human, Pair 1
KW - Chromosomes, Human, Pair 8
KW - Cohort Studies
KW - Colorectal Neoplasms
KW - Dual-Specificity Phosphatases
KW - European Continental Ancestry Group
KW - Female
KW - Genetic Loci
KW - Genome, Human
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Male
KW - Middle Aged
KW - Mitogen-Activated Protein Kinase Phosphatases
KW - Odds Ratio
KW - Polymorphism, Single Nucleotide
KW - Principal Component Analysis
KW - Risk Factors
KW - Spain
U2 - 10.1186/1471-2164-14-55
DO - 10.1186/1471-2164-14-55
M3 - Article
C2 - 23350875
SN - 1471-2164
VL - 14
SP - 55
JO - BMC Genomics
JF - BMC Genomics
ER -