Asociación Española
de Gastroenterología
Oncología Digestiva

Sabela Carballal Ramil

El grupo de trabajo de oncología de la Asociación Española de Gastroenterología (AEG) incluye a todos los socios y socias de AEG que comparten su interés por el conocimiento del cáncer gastrointestinal, incluyendo las formas hereditarias y de alto riesgo asociadas a estos tumores. La filosofía del grupo es promover la investigación colaborativa, impulsar las actividades formativas y fomentar la docencia relacionada con esta área de la especialidad de Aparato Digestivo.

Meta-analysis of mismatch repair polymorphisms within the cogent consortium for colorectal cancer susceptibility.

Autores: Picelli S, Lorenzo Bermejo J, Chang-Claude J, Hoffmeister M, Fernández-Rozadilla C, Carracedo A, Castells A, Castellví-Bel S; Memebers of EPICOLON Consortium-Gastrointestinal Oncology Group of the Spanish Gastroenterological Association, Naccarati A, Pard

Referencia: PLoS One. 2013 Sep 6;8(9):e72091. PubMed PMID: 24039736.


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.