An international team of researchers led by Dr. Richard Houlston of The Institute of Cancer Research in the United Kingdom have found a common genetic variation that plays a direct role in the development of colorectal cancer. Colorectal cancer is the second most common type of internal cancer in Australians, so the need to develop more accurate screening strategies along with improving the success rate of existing therapies is obvious.
These researchers recently found chromosome 18 to be associated with colorectal cancer in a genome-wide association study (GWAS), a technique that scans the genome for known common genetic variants also known as single nucleotide polymorphisms (SNPs) that are more prevalent in patients with a specific disease. They sequenced the area of DNA surrounding these markers and identified all variants located in this chromosomal region common to colorectal patients. Focusing on the variant most strongly associated with colorectal cancer, they found that it lies in a DNA sequence that is conserved in many other species. The xenopus frog was one of these species and so was used as the organism to test the biological consequences of this SNP. Houlston and his colleagues found the SNP causes the expression of a gene called SMAD7 to decrease. SMAD7 is an inhibitory regulator of TGF beta signalling, when cellular levels of the gene are down critical signalling events could be set into motion, moving on the path to cancer.
Disruption of SMAD7 expression had already been thought to have some role in the progression of colorectal cancer, this knowledge and the observations of this group supports a direct role for SMAD7 in cancer progression, and most likely the causal basis for colorectal cancer risk associated with this chromosomal region. By identifying the causal variants and understanding the biological basis for cancer risk associated with those variants, researchers will be able to develop better detection and diagnostic tools and more effective therapies for patients.
References:
Cold Spring Harbor Laboratory (2009, April 23). Beyond Associations: Colorectal Cancer Culprit Found. ScienceDaily. http://www.sciencedaily.com/releases/2009/04/090423180227.htm
CSIRO website. Colorectal cancer and gut health. http://www.csiro.au/science/Colorectal-Cancer-And-Gut-Health.html#why
Jessica Pickford (s42039091)
