Researchers have recently found a genetic mutation that makes some individuals more prone to colorectal, bowel and other cancers.
Scientists at the University of New South Wales (UNSW) and the University of Western Australia
studied a large family that developed colorectal cancer while young. They found
that several members of that family, belonging to three generations, had their
anti-cancer gene MLH1 switched off.
It is interesting to note that none of the members reported mutations in oncogenes normally linked with cancer.
The researchers have stumbled upon a new mechanism that increases
a person's susceptibility to cancer. In three generations of the family that
they studied, the researchers had discovered that minute changes found near the anticancer gene MLH1 acted as magnets to attract
modifying "biochemical tags," to the gene itself,
thereby switching it off.
The subtle changes caused methyl groups to be added (in a process called "methylation") to the MLH1 gene prompting them to switch off.
This change followed a familial pattern of inheritance
making the members carrying the mutation to be more susceptible to cancer.
Says study co-leader and head of the adult cancer program at the
Lowy Cancer Research Centre, Professor Robyn Ward. "When the methylation
attaches to the MLH1 gene in these families, it causes it to be completely
switched off and as a consequence cancer develops. But until now, we did not
understand how these methylation tags were being passed from parent to
Oncogenes and anti-oncogenes (anti-cancer genes) are naturally
present in our DNA. A mutation in the oncogene often results in cancer, while
the role of the anti-cancer gene is to monitor the human system for cancer.
When anti- cancer genes are 'switched off' the chances of a person developing
cancer is quite high.
Professor Robyn Ward
says this research is "very exciting" as it reveals a new way cancer
"While we were
always suspicious that these individuals probably have underlying spelling
mistakes in their DNA, we hadn't actually been able to find the exact spelling
mistake that was causing the cancer," she said.
mistake was, in fact, very subtle and something that we would not normally have
paid too much attention to, partly because it wasn't actually within the body
of the gene itself."
that the discovery could help to identify families at risk of hereditary
cancers, and possibly create a mode of treatment that allowed drugs to dispense
with the biochemical tag and "switch on" the anti-cancer gene.
UNSW's Dr Megan
Hitchins who led the study says, "This subtle spelling mistake in front of the
gene literally served like a magnet to attract a biochemical called
"methylation" which then turns the gene off. But in this family, attracting the
methylation to sit on top of their gene and turn it off is actually an error,
because that gene, because of its anti-cancer properties, is meant to be
The findings of this study have been reported in the international
journal Cancer Cell