Genome-wide Association Studies Meet Chemoprevention
Menée sur 840 patients atteints d'un cancer colorectal et sur 1 686 témoins, cette étude évalue l'association entre l'utilisation régulière d'aspirine et le risque de développer la maladie en fonction de la présence ou non du polymorphisme à simple nucléotide
A disappointment of genome-wide association studies (GWASs) applied to colorectal and other cancer risk has been the challenge of translating the observed small effects of individual genetic variants to immediate clinical application. The lackluster impact has in many ways detracted from the promise of GWASs, which includes a genetic strategy to gain some insight on component traits of complex adult-onset diseases in man. In this issue of the Journal (1), Nan et al. remind us of the potential of GWASs to advance our understanding of the genetic basis of colorectal cancer prevention, providing observational and functional evidence for an aspirin-response allelic variant.
The T variant at rs6983267 on 8q24 is a weakly protective allele for colorectal cancer discovered in the conduct of GWASs (2–4). This locus resides in an apparent enhancer domain for MYC (5), and deletion of the region in mice has been associated with resistance to APCmin-induced intestinal tumorigenesis (6) by decreasing TCF7L2 interaction with CTNNB1 (TCF4/
β-catenin)
–mediated transactivation of the MYC oncogene (5). Separately, the protective …
Journal of the National Cancer Institute , éditorial, 2013