New genetic variant increasing risk of bowel cancer identified
23 Sept 2010
A single variant in a person’s DNA can promote bowel cancer
development, according to an international study led by scientists at
The Institute of Cancer Research (ICR).
A slight change in a genetic variant called rs16888589 — an ‘A’ in
the DNA code rather than a ‘G’ — produces more protein from a gene
called EIFH3. Importantly, the team showed that high levels of the
EIFH3 protein lead to the development of bowel cancer.
Lead researcher Professor Richard Houlston, from the ICR, says: “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.
“It’s interesting that even a single change to the DNA sequence can
alter how much protein is produced and increase the risk of this
disease. Finding proteins involved in cancer development is crucial,
as they are potential targets for new drugs.”
Genome-wide association studies have previously identified fourteen
DNA variants that each increase a person’s risk of bowel cancer by
between 1.5- and 2-fold. Inheriting more than one variant increases
the risk even further. These variants, called single nucleotide
polymorphisms (SNPs), are a single-letter change in the DNA code.
These genetic screens identify variants that are linked to the
disease, but are not necessarily responsible for causing the
disease. For example, the variants may just be inherited at the same
time as the key DNA. So 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.
The starting point for the study was a variant on chromosome 8q23
that Professor Houlston’s team has previously shown increased bowel
cancer risk by up to a 1.5-fold.
In a study partly funded by Cancer Research UK, scientists at the
ICR 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 how one of these four variants called
rs16888589 caused a change in the amount of protein produced by
Dr Lesley Walker, Cancer Research UK’s director of science
information, said: “This study is another important step towards
understanding the gene faults that put some people at greater risk
of bowel cancer, and it also gives us clues to how the disease
develops. Research like this opens up new possibilities for
identifying people with a higher risk of bowel cancer, and for
developing new treatments that target cancers with particular