TY  - JOUR
A1  - Pittman, Alan M.
A1  - Naranjo, Silvia
A1  - Webb, Emily
A1  - Broderick, Peter
A1  - Lips, Esther H.
A1  - van Wezel, Tom
A1  - Morreau, Hans
A1  - Sullivan, Kate
A1  - Fielding, Sarah
A1  - Twiss, Philip
A1  - Vijayakrishnan, Jayaram
A1  - Casares, Fernando
A1  - Qureshi, Mobshra
A1  - Gómez-Skarmeta, José Luis
A1  - Houlston, Richard S.
T1  - The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression
Y1  - 2009/06/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 987 
EP  - 993 
DO  - 10.1101/gr.092668.109 
VL  - 19 
IS  - 6 
UR  - http://genome.cshlp.org/content/19/6/987.abstract 
N2  - 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. 
ER  -