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Aldehydes, a common class of chemicals found
everywhere from car exhausts, smoke, building
materials and furniture to cosmetics and shampoos
could increase cancer risk because of their ability
to break down the repair mechanisms that prevent
faults in our genes, according to a study published
today in the journal Cell.
Aldehydes are a class of chemicals made in our own
bodies in small quantities but increasingly found
everywhere in our environment.
Exposure to these chemicals has previously been
linked with cancer, but the reasons for the link
remain unclear.
New research led by Professor Ashok Venkitaraman,
Director of the Medical Research Council Cancer Unit
at the University of Cambridge, has used
genetically-engineered human cells and cells from
patients bearing a faulty copy of the breast cancer
gene BRCA2 to identify the mechanism by which
exposure to aldehydes could promote cancer.
Damage to our DNA, which arises frequently as cells
in our bodies divide, can lead to the development of
cancers, but our body has its own defence mechanism
that helps repair this damage.
However, Professor Venkitaraman and colleagues found
that aldehyde exposure breaks down this defence
mechanisms even in normal healthy cells, but people
who have inherited a faulty copy of BRCA2 are
particularly sensitive to such damage.
Everyone is born with two copies of most genes.
People who inherit a single faulty copy of the BRCA2
gene are susceptible to cancer.
The reason why is not fully understood, because
their cells should be able to repair DNA using the
lower – but still adequate – levels of BRCA2 protein
made from the remaining, intact copy of the gene.
This new study shows that aldehydes trigger the
degradation of BRCA2 protein in cells.
In people who inherit one faulty copy of the BRCA2
gene, this effect pushes down BRCA2 protein levels
below the amount required for adequate DNA repair,
breaking down the normal mechanisms that prevent
mutations, which could promote cancer formation.
Around one in 100 people may carry a faulty BRCA2
gene, putting them at risk of developing breast,
ovarian, prostate and pancreatic cancer. Exposure to
aldehydes could increase their chances of developing
these cancers.
“Our study shows how chemicals to which we are
increasingly exposed in our day-to-day lives may
increase the risk of diseases like cancer,” says
Professor Venkitaraman.
“It also helps to explain why ‘the faults in our
stars’ – namely the faulty genes we are born with –
could make some people particularly sensitive to the
cancer-causing effects of these chemicals.
“An important implication of our work is that it may
be aldehyde exposure that triggers cancer
susceptibility in people who inherit one faulty copy
of the BRCA2 gene. This may help us in future to
prevent or treat cancer in such people.”
One common potential source of aldehydes is alcohol:
our body converts the alcohol that we drink into
acetaldehyde, one such chemical.
Ordinarily, this is broken down by a natural enzyme
known as acetaldehyde dehydrogenase, but over 500
million people mainly from countries such as Japan,
China and Korea inherit a faulty gene, ALDH2, that
inactivates this enzyme.
This is why many Asian people develop flushes when
they drink, but could mean they are also
particularly sensitive to the cancer-promoting
effect.
This new research shows that aldehyde accumulation
in such people could trigger cancer susceptibility
by degrading BRCA2, compromising DNA repair, whether
or not they inherit a faulty copy of BRCA2. An
estimated 30-60% of people from Japan, Korea and
China carry the faulty ALDH2 and may therefore be at
risk from cancer through this new mechanism.
For more information
Tan, SLW et al. A class of environmental and
endogenous toxins induces BRCA2 haploinsufficiency
and genome instability. Cell; 1 Jun 2017; DOI:
10.1016/j.cell.2017.05.010
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University of Cambridge
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