Variant decreases SMAD7 gene expression, which has been linked to disease risk, according to paper in Genome Research.

Scientists report finding a genetic variant that is associated with colorectal cancer risk. They found that this SNP alters the expression of SMAD7, which has been implicated in the progression of the disease.

Investigators from the Institute of Cancer Research, Centro Andaluz del Biologia del Desarollo, and Leiden University collaborated on this study. Findings are reported online in Genome Research in a paper titled “The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression.”

The group previously linked variants on chromosome 18 to colorectal cancer through a genome-wide association study. In the current research, they were trying to understand the biology behind these SNPs. They sequenced the region of DNA surrounding these markers in a large group of colorectal cancer cases and controls, identifying all variants residing in this chromosomal region common to colorectal cancer patients.

They then focused on the novel variant most strongly associated with colorectal cancer and found that it resides in a DNA sequence that is conserved in many other species. They were thus able to use xenopus frogs as a model organism to test the biological consequences of this SNP.

The group found that the SNP decreases the expression of a nearby gene called SMAD7. This gene is an inhibitory regulator of TGF-beta signaling. If cellular levels of SMAD7 are down, signaling events could be set into motion that lead the cell on a path to cancer. Disrupting SMAD7 expression has previously been associated with progression of colorectal cancer.

Past Findings in Colorectal Cancer
Prognostic Biomarker for Colorectal Cancer Found in Lymph Node (Feb. 18, 2009)
Levels of Two Proteins Found to Predict Death Risk in Patients with Surgically Removed Colorectal Cancer (Dec. 9, 2008)
BRAF Mutation Found to Confer Resistance to EGFR Inhibitors in Colorectal Cancer Patients (Oct. 23, 2008)
SNP Linked to Reduced Risk of Colorectal Cancer (Oct. 1, 2008)
Scientists Link Stem Cell Protein to Heightened Tumor Progression in Colorectal Cancer (Aug. 20, 2008)

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