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Beyond associations: Colorectal cancer culprit found
Date:4/23/2009

r, and found that it resides in a DNA sequence that is conserved in many other species so well conserved that they were able to use xenopus frogs as a model organism to test the biological consequences of this SNP. The group found that the SNP causes the expression of a nearby gene, called SMAD7, to decrease. SMAD7 is an inhibitory regulator of TGF-beta signaling. If cellular levels of SMAD7 are down, critical signaling events could be set into motion, leading the cell on the path to cancer. This result is particularly important because disruption of SMAD7 expression has been previously implicated in progression of colorectal cancer. Taken together with this knowledge, their observation supports a direct role for SMAD7 in cancer progression, and very likely the causal basis for colorectal cancer risk associated with this chromosomal region.

Houlston explained, "Our efforts show that many different methodologies are required to close in and identify disease-causing variants identified through genome-wide association studies." Their work specifically exemplifies the combination of genetic and functional analyses, including regenotyping, resequencing, and use of model organisms, needed to approach the biological mechanism of cancer. By identifying the true causal variants and understanding the biological basis for cancer risk associated with those variants, researchers will be able to design better screening strategies and more effective therapies for patients.


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Contact: Peggy Calicchia
calicchi@cshl.edu
516-422-4012
Cold Spring Harbor Laboratory
Source:Eurekalert

Page: 1 2

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