London: Scientists have discovered that genetic `switches`, which regulate the expression of genes, play a major role in the development of cancer.Researchers at the Karolinska Institutet in Sweden and the University of Helsinki in Finland investigated a gene region that contains a particular single nucleotide variant associated with increased risk for developing colorectal and prostate cancers.The study found that removing this region caused dramatic resistance to tumour 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. 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 on mice, scientists have analysed 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.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 tumour formation.The removed gene region thus appears to act as an important gene switch promoting cancer, and without it tumours 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.
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