Scientists Unravel Genetic Risk of Bowel Cancer
16 September 2010 - An international study led by scientists at The Institute of Cancer Research (ICR) has shown how a single variant in a person’s DNA can promote bowel cancer development.
Professor Richard Houlston’s team previously found a genetic variant on chromosome 8q23 that increased bowel cancer risk by up to 1.5-fold, using a genome wide association study. These genetic screens identify single letter changes in the DNA code that are linked to the disease, but are not necessarily responsible for causing the disease. To fully understand the biological process that leads to the development of cancer, scientists need to find the causative – and not the associated – genetic change.
In this study, the team re-sequenced 22,000 bases (letters) of DNA around the variant and identified all of the single letters in this region that differed between individuals.
More than 100 variants were found and these were examined in 2,000 people with bowel cancer and 2,000 people without the disease. Four SNPs stood out. All were located near a gene called EIFH3, in a region of DNA believed to be involved in switching the gene on or off. Further studies showed that a change in one of these four variants – from an A letter to a G letter at position rs16888589 – caused an increase in the amount of protein produced by EIFH3.
Importantly, the team then showed that high levels of the eifh3 protein lead to bowel cancer growth.
“We know from other cancers that too much of the protein eifh3 leads to an increase in cell proliferation, growth and survival, but this is the first confirmation it is involved in bowel cancer development,” Professor Houlston said.
