-
Research follows up previous mapping studies to unearth
genes associated with increased risk of breast
cancer
-
More than 30 of the genes are linked to breast cancer
survival and could be targets for new drugs
Scientists have linked 110 genes to an increased risk of breast
cancer in the most comprehensive study ever to unpick the
genetics of the disease.
Their study used a pioneering genetic technique to analyse maps
of DNA regions linked to an inherited risk of breast cancer and
identify the actual genes involved in raising a woman’s risk.
Researchers also linked 32 of the new genes to the length of time
women survived breast cancer – suggesting these could be
important in the development of the disease and potential targets
for future treatments.
Scientists at The Institute of Cancer Research, London, looked in
detail at 63 areas of the genome that had previously been
associated with the risk of breast cancer by mapping studies.
Finding the genes responsible for the increased risk is not
straightforward because small sequences of DNA can interact with
completely different parts of the genome through a strange
phenomenon known as ‘DNA looping’.
But the researchers, funded by Breast Cancer Now, used a
technique they developed called Capture Hi-C to study
interactions between different regions of the genome.
The study – published today (Monday) in Nature
Communications – uncovered which specific genes were
involved and how that might increase a woman’s risk of developing
breast cancer.
The team at the Breast Cancer Now Toby Robins Research Centre at
The Institute of Cancer Research (ICR) found that some of the 63
regions of the genome were physically interacting with genes more
than a million letters of DNA code away.
They were able to identify 110 new genes that could potentially
be causing an increased risk of breast cancer across 33 of the
regions they studied. In the remaining 30 areas, they were unable
to find any specific genes.
One third of the target genes for which they had patient data –
32 out of 97 – were also linked to survival in women with
oestrogen receptor-positive breast cancer, suggesting they play
an important role in the disease.
In the future, testing for these genes could help pick out women
who are most at risk of developing the disease – or they could be
explored as targets for new drugs.
Scientists at the ICR – a research institute and charity –
studied DNA loops in cells from four different types of breast
cancer and normal, healthy cells to find out which genes were
consistently involved in looping interactions.
Most of the 110 genes found in the study had not been linked to
breast cancer risk before, and further work will be needed to
determine the extent of their role in the disease.
One of these, called FADD, has previously been
linked to head and neck cancer and lung cancer and could be a
promising target for new cancer therapies.
Previous large-scale genetics studies have implicated 14 of the
110 genes as playing a role in breast cancer risk, such as the
oestrogen receptor gene ESR1, showing that Capture
Hi-C is an effective tool for picking up risk genes.
Dr Olivia Fletcher, Team Leader in Functional Genetic
Epidemiology at The Institute of Cancer Research, London,
said:
“Our study took the high-level maps of breast cancer risk regions
and used them to pull out specific genes that seem to be
associated with the disease.
“We studied how DNA forms loops to allow physical interactions
between a DNA sequence in one part of the genome and a risk gene
in another.
“Identifying these new genes will help us to understand in much
greater detail the genetics of breast cancer risk. Ultimately,
our study could pave the way for new genetic tests to predict a
woman’s risk, or new types of targeted treatment.”
Baroness Delyth Morgan, Chief Executive at Breast Cancer
Now, which funded the study, said:
“These are really important findings. We urgently need to unravel
how the genetic changes in the building blocks of our DNA
influence a woman’s risk of breast cancer, and this study adds
another vital piece to this jigsaw.
“More women are now being diagnosed with breast cancer than ever
before, and these crucial findings could ultimately help us more
accurately predict who is most at risk and develop new targeted
treatments.
“Many of these genes have been relatively undocumented to date
and we now hope further research will untangle their exact role
in breast cancer risk, and how we could use them to stop more
women developing the disease.”
Professor Paul Workman, Chief Executive of The Institute
of Cancer Research, London, said:
“Large-scale genomic studies have been instrumental in
associating areas of our DNA with an increased risk of breast
cancer. This study brings these regions of DNA into sharper
focus, uncovering a treasure trove of genes that can now be
investigated in more detail.
“The ways in which particular genes influence cancer risk are
highly complex. In the future, a better understanding of the
genes identified in this study could lead to the discovery of new
targeted drugs, or new strategies to improve diagnosis or
prevention of the disease.”
