A simple blood test is currently in development that could help
predict the likelihood of a woman developing breast cancer, even in
the absence of a high-risk BRCA1 gene mutation, according to new
UCL research.
The research identifies an epigenetic signature in the blood of
women predisposed for breast cancer owing to an inherited genetic
mutation of the BRCA1 gene. Epigenetic alterations are thought to
be key molecular switches that are involved in the development of
cancer. Strikingly, the same signature was discovered in the blood
of women without a BRCA1 mutation but who went on to develop breast
cancer, making it a potential early marker of women's cancer in the
general population.
BRCA1 mutation is inherited from a parent, and is the cause of
at least 10 per cent of breast cancers. The cause of the remaining
90 per cent of sporadic breast cancers in non-mutation carriers
remains to be explained. Scientists are beginning to understand
that genetic mutations are not the sole contributors to disease
development and that the way in which genes are arranged in our
cells can affect whether they function appropriately - that is,
whether they are turned on or off. The arrangement and expression
of our genes is overseen by the process of epigenetics. One of the
most studied epigenetic mechanisms is a process called DNA
methylation, which was the focus of the current study.
The researchers used blood samples collected several years
before breast cancer development from two large UK cohorts of women
- the MRC National Survey of Health and Development and the UK
Collaborative Trial of Ovarian Cancer Screening. They looked at the
DNA methylation signature from blood of those women with and
without BRCA1 mutations. When this signature was applied to samples
from both these groups, those women who developed non-hereditary
cancers were found to have the same DNA methylation signature.
Professor Martin Widschwendter, head of the UCL Department of
Women's Cancer, said: "We identified an epigenetic signature in
women with a mutated BRCA1 gene that was linked to increased cancer
risk and lower survival rates. Surprisingly, we found the same
signature in large cohorts of women without the BRCA1 mutation and
it was able to predict breast cancer risk several years before
diagnosis."
The researchers believe the epigenetic signature they found is
consistent with the idea that changes in the epigenome of immune
cells are key to cancer progression. The signature may be
responsible for silencing genes in immune cells, which in turn
could affect the ability of the immune system to prevent breast
cancer development. Further research needs to be done to find out
whether this epigenetic signature is just an indicator of breast
cancer risk or is involved with the progression of breast cancer.
Work is now proceeding on using these findings in the clinical
setting.
Professor Widschwendter said: "The data is encouraging since it
shows the potential of a blood based epigenetic test to identify
breast cancer risk in women without known predisposing genetic
mutations."
The work was jointly funded by The Eve Appeal and the National
Institute for Health Research (NIHR) University College London
Hospitals Biomedical Research Centre.
The paper, A
BRCA1-mutation associated DNA methylation signature in blood cells
predicts sporadic breast cancer incidence and survival, is
published in Genome Medicine.