期刊
PLOS ONE
卷 8, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0072091
关键词
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资金
- Spanish National Genotyping Center (CEGEN-ISCIII)-USC
- UPF
- Institutional Tumor Bank of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- Instituto de Salud Carlos III, Spanish Ministry of Health [FIS PI08-1635, PS09-1037]
- Cancer Research UK Programme Grant [C348/A12076]
- Centre Grant from the CORE Charity
- Hunter Medical Research Institute
- Priority Research Centre for Information Based Medicine
- German Research Council, German Federal Ministry of Research and Education
- Baden Wurttemberg State Ministry of Research, Science and Arts
- Fondo de Investigacion Sanitaria/FEDER [08/0024, 08/1276, PS09/02368, 11/00219, 11/00681]
- Instituto de Salud Carlos III (Accion Transversal de Cancer), Xunta de Galicia [RHI07/04, 08CSA005208PR]
- Ministerio de Ciencia e Innovacion [SAF2010-19273]
- Asociacion Espanola contra el Cancer (Fundacion Cientifica y Junta de Barcelona)
- Fundacio Olga Torres
- FP7 CHIBCHA Consortium
- Instituto de Salud Carlos III
- Deutsche Forschungsgemeinschaft (DFG) [SFB/TRR77, Z2]
- National Cancer Institute [R01 CA136726]
- German Ministry for Education and Research through the German National Genome Research Network (NGFNplus) Colon Cancer Network (CCN)
- [GAP304/10/1286]
- [GA310/07/1430]
- MRC [MC_PC_U127527198, MC_U127527198] Funding Source: UKRI
- Cancer Research UK [12076] Funding Source: researchfish
- Chief Scientist Office [CZB/4/449] Funding Source: researchfish
- Medical Research Council [MC_PC_U127527198, MC_U127527198] Funding Source: researchfish
- Worldwide Cancer Research [12-1087] Funding Source: researchfish
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.
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