Scientists at Karolinska Institutet in Sweden and the University of Helsinki in Finland have shown that the "switches" that regulate the expression of genes play a major role in the development of cancer. In a study, published in Science, they have investigated a gene region that contains a particular single nucleotide variant associated with increased risk for developing colorectal and prostate cancers – and found that removing this region caused dramatic resistance to tumor formation.
Genome-wide association studies have revealed genomic regions associated with more than 200 diseases, including heart disease, diabetes and different types of cancer. The unveiled human genetic variation has attracted much attention in both scientific and popular press. However, the mechanisms by which these genomic regions act are not fully understood. One suggestion that has generated considerable interest is the possibility that the risk polymorphisms located far from genes could function as gene regulatory elements or "switches" that regulate the expression of genes.
In the current study, which was conducted in mice, scientists have analyzed one particular single nucleotide variant in a region associated with increased risk for developing colorectal and prostate cancers, but whose mechanism of action has been unclear. Although this variant increases cancer risk only by 20 per cent, it is very common and therefore accounts for more inherited cancer than any other currently known genetic variant or mutation.
The scientists removed the gene region containing the risk variant from the mouse genome, and found that as a result the mice were healthy but displayed a small decrease in the expression of a nearby cancer gene, called MYC. However, when these mice were tested for the ability to form tumours after activation of an oncogenic signal that causes colorectal cancer in humans, they showed dramatic resistance to tumor formation. The removed gene region thus appears to act as an important gene switch promoting cancer, and without it tumors develop much more rarely.
According to the scientists, these results show that although the gene variants – which make individual humans different from each other – in general have a small impact on disease development, the gene switches in which they reside can play a major role.
"Our study also highlights that growth of normal cells and cancer cells is driven by different gene switches, suggesting that further work to find ways to control the activity of such disease-specific switches could lead to novel, highly specific approaches for therapeutic intervention", says Professor Jussi Taipale, who led the study.
Publication: "Mice Lacking a Myc Enhancer Element that Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors", Sur, I., Hallikas, O., Vähärautio, A., Yan, J., Turunen, M., Enge, M., Taipale, M., Karhu, A., Aaltonen, L. A., and Taipale, J., Science, in press, online 1 November 2012.
Karolinska Institutet: http://info.ki.se/ki
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Doctors have used perfect replicas of childrens' hearts to uncover and repair hidden defects
An experiment testing people’s altruism in the face of electric shocks is clear on one thing: we are drawn to these little blasts
Researchers gear up tests in West Africa to see whether blood from Ebola survivors can help people who are sick with the disease. This is part of a broader effort to test therapies in West Africa.
The virus's foray into Europe coincides with peak production of Christmas turkeys, the poultry species most vulnerable to bird flu
A novel kind of nanoparticle could lead to more effective cancer treatments.Patients and doctors often don’t know if surgery to remove cancerous tissue was successful until scans are performed months later. A new kind of nanoparticle could show patients if they’re in the clear much earlier.
One challenge in evaluating the effectiveness of different medical procedures, is that patients behave differently after different procedures. Is this true for patients getting heart surgery?
It is only in the aftermath of treatment that survivors discern that their adrenalin alone wont fuel the rest of their recovery. For many, surviving cancer is followed by even more hardship
Just down the road from Facebook and Google, Dr. Phil Wagner runs a laboratory dedicated to optimizing the performance of some of the world's top athletes. At Sparta Performance Science in Menlo Park, California, Wagner and his team bring the spirit of Silicon Valley to bear on the athletic world, helping athletes find the tiny advantages that add to championships. Join us for a trip inside the lab to see where sports meets science.
Pieter Cohen, an internist in Massachusetts, got interested in dietary supplements several years ago, when some of his …
The risk of overdiagnosis and false positives means the UK may be barking up the wrong tree in trialling a wider target age range for breast screening