Multiple Functional Risk Variants in a SMAD7 Enhancer Implicate a Colorectal Cancer Risk Haplotype
作者： Barbara K Fortini , Stephanie Tring , Sarah J Plummer , Christopher K Edlund , Victor Moreno
DOI: 10.1371/JOURNAL.PONE.0111914
关键词:
摘要: Genome-wide association studies (GWAS) of colorectal cancer (CRC) have led to the identification a number common variants associated with modest risk. Several risk map within vicinity TGFβ/BMP signaling pathway genes, including rs4939827 an intron SMAD7 at 18q21.1. A previous study implicated novel SNP (novel 1 or rs58920878) as functional variant enhancer element in 4. In this study, we show that four SNPs (rs6507874, rs6507875, rs8085824, and linkage disequilibrium (LD) index demonstrate allele-specific effects large, multi-component SMAD7. All protein binding nuclear extracts CRC cell lines. Furthermore, some risk-associated alleles correlate increased expression normal colon tissues. Finally, is responsive BMP4 stimulation. Taken together, propose 18q21.1 due regulate potentially perturb BMP negative feedback loop pathways.
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