Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility
Por:
Picelli, S, Bermejo, JL, Chang-Claude, J, Hoffmeister, M, Fernandez-Rozadilla, C, Carracedo, A, Castells, A, Castellvi-Bel, S, Naccarati, A, Pardini, B, Vodickova, L, Muller, H, Talseth-Palmer, BA, Stibbard, G, Peterlongo, P, Nici, C, Veneroni, S, Li, L, Casey, G, Tenesa, A, Farrington, SM, Tomlinson, I, Moreno, V, van Wezel, T, Wijnen, J, Dunlop, M, Radice, P, Scott, RJ, Vodicka, P, Ruiz-Ponte, C, Brenner, H, Buch, S, Volzke, H, Hampe, J, Schafmayer, C, Lindblom, A, González Juan D., Roman, E, Ramon, T., Poca, M, Concepcion, Ma M., Martin, M, Pétriz L., EPICOLON Consortium
Publicada:
6 sep 2013
Resumen:
In the last four years, Genome-Wide Association Studies (GWAS) have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC). Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a follow-up of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimated recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H), decreased from 1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to 1.08 in the initial meta-analysis. Since the corresponding summary probability value was 0.06, we decided to retrieve additional information for this polymorphism. The incorporation of six further studies resulted in around 13000 cases and 13000 controls. The newly updated OR was 1.03. The results from the present large, multicenter study illustrate the possibility of decreasing effect sizes with increasing samples sizes. Phenotypic heterogeneity, differential environmental exposures, and population specific linkage disequilibrium patterns may explain the observed difference of genetic effects between Sweden and the other investigated cohorts.
Filiaciones:
Picelli, S:
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden
Ludwig Inst Canc Res, Stockholm Branch, S-10401 Stockholm, Sweden
Bermejo, JL:
Univ Heidelberg Hosp, Inst Med Biometry & Informat, Heidelberg, Germany
German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany
Chang-Claude, J:
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Hoffmeister, M:
German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany
Fernandez-Rozadilla, C:
Univ Santiago de Compostela, Hosp Clin, Genom Med Grp, CIBERER,FPGMX, Galicia, Spain
Carracedo, A:
Univ Santiago de Compostela, Hosp Clin, Genom Med Grp, CIBERER,FPGMX, Galicia, Spain
Castells, A:
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBEREHD,IDIBAPS, Barcelona, Spain
Castellvi-Bel, S:
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBEREHD,IDIBAPS, Barcelona, Spain
Naccarati, A:
Acad Sci Czech Republic, Inst Expt Med, Prague, Czech Republic
Pardini, B:
Acad Sci Czech Republic, Inst Expt Med, Prague, Czech Republic
Vodickova, L:
Acad Sci Czech Republic, Inst Expt Med, Prague, Czech Republic
Charles Univ Prague, Fac Med 1, Prague, Czech Republic
Muller, H:
German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany
Talseth-Palmer, BA:
Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia
Hunter Med Res Inst, Newcastle, NSW, Australia
Stibbard, G:
Univ Newcastle, Sch Sci & IT, Newcastle, NSW 2300, Australia
Peterlongo, P:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy
Nici, C:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy
Ist FIRC Oncol Mol, Fdn IFOM, Milan, Italy
Veneroni, S:
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy
Li, L:
Case Western Reserve Univ, Case Comprehens Canc Ctr, Case Ctr Transdisciplinary Res Energet & Canc, Dept Family Med, Cleveland, OH 44106 USA
Casey, G:
Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA
Tenesa, A:
Univ Edinburgh, Inst Genet & Mol Med, Colon Canc Genet Grp, Edinburgh, Midlothian, Scotland
MRC Human Genet Unit, Edinburgh, Midlothian, Scotland
Tomlinson, I:
Oxford NIHR Comprehens Biomed Res Ctr, Oxford, England
Moreno, V:
CIBERESP, IDIBELL, ICO, Barcelona, Spain
Univ Barcelona, Hosp Llobregat, Barcelona, Spain
van Wezel, T:
Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands
Wijnen, J:
Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands
Radice, P:
Ist FIRC Oncol Mol, Fdn IFOM, Milan, Italy
Scott, RJ:
Hunter Med Res Inst, Newcastle, NSW, Australia
John Hunter Hosp, Hunter Area Pathol Serv, Div Genet, Newcastle, NSW, Australia
Vodicka, P:
Charles Univ Prague, Fac Med 1, Prague, Czech Republic
Brenner, H:
German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany
Buch, S:
Univ Hosp Schleswig Holstein, Dept Gen Internal Med, Kiel, Germany
Volzke, H:
Univ Med Greifswald, Inst Community Med, Greifswald, Germany
Hampe, J:
Univ Hosp Schleswig Holstein, Dept Gen Internal Med, Kiel, Germany
Schafmayer, C:
Univ Kiel, Dept Gen & Thorac Surg, Kiel, Germany
Lindblom, A:
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden
González Juan D.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Roman, E:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Ramon, T.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Poca, M:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Concepcion, Ma M.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Martin, M:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Pétriz L.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Gold, Green Published
|