A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12
Por:
Fernandez-Rozadilla, C, Cazier, JB, Tomlinson, IP, Carvajal-Carmona, LG, Palles, C, Lamas, MJ, Baiget, M, Lopez-Fernandez, LA, Brea-Fernandez, A, Abuli, A, Bujanda, L, Clofent, J, Gonzalez, D, Xicola, R, Andreu, M, Bessa, X, Jover, R, Llor, X, Moreno, V, Castells, A, Carracedo, A, Castellvi-Bel, S, Ruiz-Ponte, C
Publicada:
26 ene 2013
Resumen:
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 (P-replication=0.042; P-pooled=5.523x10(-03); OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (P-replication=0.039; P-pooled=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.
Filiaciones:
Fernandez-Rozadilla, C:
Galician Publ Fdn Genom Med FPGMX, Grp Med Xenom, Ctr Invest Biomed Red Enfermedades Raras CIBERer, IDIS, Santiago De Compostela 15706, Spain
Cazier, JB:
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
Tomlinson, IP:
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
Univ Oxford, NIHR Comprehens Biomed Res Ctr, Oxford OX3 7BN, England
Carvajal-Carmona, LG:
Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Davis, CA 95616 USA
Palles, C:
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
Lamas, MJ:
CHUS, Oncol Pharm Unit, Santiago De Compostela 15706, Spain
Baiget, M:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
Lopez-Fernandez, LA:
Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Gregorio Maranon, Pharmacogenet & Pharmacogen Lab, Serv Farm, Madrid 28007, Spain
Brea-Fernandez, A:
Galician Publ Fdn Genom Med FPGMX, Grp Med Xenom, Ctr Invest Biomed Red Enfermedades Raras CIBERer, IDIS, Santiago De Compostela 15706, Spain
Abuli, A:
Hosp del Mar, Dept Gastroenterol, Barcelona 08003, Spain
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBERehd,IDIBAPS, E-08036 Barcelona, Spain
Bujanda, L:
Univ Basque Country, Dept Gastroenterol, Donostia Hosp, CIBERehd, San Sebastian 20014, Spain
Clofent, J:
Hosp Meixoeiro, Dept Gastroenterol, Vigo 36214, Spain
Hosp Sagunto, Dept Internal Med, Sect Digest Dis, Valencia 46520, Spain
Gonzalez, D:
Hosp Santa Creu & Sant Pau, Serv Patol Digest, Barcelona 08003, Spain
Xicola, R:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL 60607 USA
Andreu, M:
Hosp del Mar, Dept Gastroenterol, Barcelona 08003, Spain
Bessa, X:
Hosp del Mar, Dept Gastroenterol, Barcelona 08003, Spain
Jover, R:
Hosp Gen Univ Alicante, Dept Gastroenterol, Alicante 03010, Spain
Llor, X:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL 60607 USA
Moreno, V:
CIBERESP, Bellvitge Biomed Res Ctr IDIBELL, Catalan Inst Oncol ICO, Canc Prevent & Control Program, Barcelona 08907, Spain
Castells, A:
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBERehd,IDIBAPS, E-08036 Barcelona, Spain
Carracedo, A:
Galician Publ Fdn Genom Med FPGMX, Grp Med Xenom, Ctr Invest Biomed Red Enfermedades Raras CIBERer, IDIS, Santiago De Compostela 15706, Spain
Castellvi-Bel, S:
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBERehd,IDIBAPS, E-08036 Barcelona, Spain
Ruiz-Ponte, C:
Galician Publ Fdn Genom Med FPGMX, Grp Med Xenom, Ctr Invest Biomed Red Enfermedades Raras CIBERer, IDIS, Santiago De Compostela 15706, Spain
Gold, Green Published
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