@article{Pittman01062009,
author = {Pittman, Alan M. and Naranjo, Silvia and Webb, Emily and Broderick, Peter and Lips, Esther H. and van Wezel, Tom and Morreau, Hans and Sullivan, Kate and Fielding, Sarah and Twiss, Philip and Vijayakrishnan, Jayaram and Casares, Fernando and Qureshi, Mobshra and Gómez-Skarmeta, José Luis and Houlston, Richard S.}, 
title = {The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression},
volume = {19}, 
number = {6}, 
pages = {987-993}, 
year = {2009}, 
doi = {10.1101/gr.092668.109}, 
abstract ={Recent genome-wide scans for colorectal cancer (CRC) have revealed the SMAD7 (mothers against decapentaplegic homolog 7) gene as a locus associated with a modest, but highly significant increase in CRC risk. To identify the causal basis of the association between 18q21 variation and CRC, we resequenced the 17-kb region of linkage disequilibrium and evaluated all variants in 2532 CRC cases and 2607 controls. A novel C to G single nucleotide polymorphism (SNP) at 44,703,563 bp was maximally associated with CRC risk (P = 5.98 × 10−7; ≥1.5-fold more likely to be causal than other variants). Using transgenic assays in Xenopus laevis as a functional model, we demonstrate that the G risk allele leads to reduced reporter gene expression in the colorectum (P = 5.4 × 10−3). Electrophoretic mobility shift assays provided evidence for the role of Novel 1 in transcription factor binding. We propose that the novel SNP we have identified is the functional change leading to CRC predisposition through differential SMAD7 expression and, hence, aberrant TGF-beta signaling.}, 
URL = {http://genome.cshlp.org/content/19/6/987.abstract}, 
eprint = {http://genome.cshlp.org/content/19/6/987.full.pdf+html}, 
journal = {Genome Research} 
}