London: DNA damage caused by
smoking can be detected in cheek swabs, finds research published today in JAMA
Oncology. The study provides evidence that smoking induces a general cancer
program that is also present in cancers which aren’t usually associated with it
– including breast and gynaecological cancers. The research team, led by
Professor Martin Widschwendter (UCL Institute for Women's Health and Dr Andrew
Teschendorff (UCL Cancer Institute) looked at epigenetic alterations – changes
to the DNA that switch genes on and off. Epigenetic changes are associated with
cancer development and can be caused by exposure to environmental factors such
as cigarette smoke.
The researchers aimed to
explore whether normal cells from the inside of the cheek would demonstrate epigenetic
changes which are associated with lung and other epithelial cancers. These
types of cancers originate in the epithelial cells – which cover the outside of
the body as skin or the inside of the body as lining for organs and body
cavities – and make up 85% of all cancer cases in the UK. The buccal cells taken
from the cheek swabs are easy to collect and are directly exposed to cigarette
smoke in those who smoke.
To do this, in collaboration with Prof Diana
Kuh (UCL Epidemiology & Public Health) and her team, they analysed buccal
samples from 790 women all born in 1946 and 152 matched blood samples from the
Medical Research Council National Survey of Health and Development. The dataset
included information about smoking history and smoking status at the time the
samples were collected.
This analysis showed that buccal cells in
women who have smoked had numerous changes to their epigenomes – known as
DNA-methylation (DNAme). Buccal cells showed a 40-fold increase in abnormal methylation
sites compared to matched blood samples, making them a more reliable indicator
of DNA changes.
Smoking-related DNA damage to the epigenome of certain genes had been reversed in ex-smokers who had quit 10 years previously before sample collection, highlighting the key health benefits of quitting smoking.
Professor Martin Widschwendter
The team then went on to analyse this
smoke-triggered epigenetic program in over 5000 tissue samples, including
normal tissue, pre-cancerous tissue and cancer tissue from 15 different
epithelial cancer types. In doing so, they tested whether they were able to
discriminate normal tissue from cancerous tissue. They found that this program
– which they originally derived in normal buccal cells of smokers – is able to
discriminate between normal and cancerous tissue with almost 100% sensitivity
and 100% specificity irrespective of the organ from which the cancer arose.
Researchers also found that the absence or
presence of this program was able to predict the fate of pre-invasive cancer lesions.
The presence of the faulty program in the cells makes it very likely that a
pre-invasive cancer will progress to a full-blown invasive cancer. However, the
absence of the faulty program makes it likely that the pre-cancer can
potentially regress and disappear.
An individuals’ DNA works like the hardware within
a cell, with the epigenome being the software. Smoking misprograms the
epigenome and the genetic code becomes difficult or impossible to read. Misprogramming
of a cells’ software, in conjunction with genetic mutations, eventually lead to
an inability of these cells to develop into specific differentiated cells.
These cells are then trapped in an undifferentiated status and can grow indefinitely
and spread into other organs.
Senior author Professor Martin Widschwendter said: “These are significant results
for our core interest which is decoding women’s cancers. We are a big step closer now to unravelling
how environmental factors cause cancer. These results pave the way for other
studies in which easily accessible cells can be used as proxies to highlight
epigenetic changes that may indicate a risk of developing cancer at a site
where cells are inaccessible. This is incredibly exciting for women’s cancers such
as ovary, breast and endometrial cancer where predicting the cancer risk is a
big challenge.”
“The results also demonstrate that smoking-related DNA damage to the epigenome
of certain genes had been reversed in ex-smokers who had quit 10 years
previously before sample collection, highlighting the key health benefits of
quitting smoking, or not taking it up at all.”
Athena Lamnisos, CEO of The Eve Appeal said:
“We know that what’s going to save most lives from gynaecological cancers is
prevention – decoding why these cancers start and stopping them. That’s why we
fund research into the earlier diagnosis, risk prediction and prevention. This
research shows how signs of developing cancer may be detected using accessible
cells from inside the mouth. It points the way for pioneering further studies
that will help detect women’s cancers.”
Lead author Dr Andrew
Teschendorff said: “Our work shows that smoking has a major impact on the
epigenome of normal cells that are directly exposed to the carcinogen. Of
particular significance is that these epigenetic changes are also seen in both
smoking-related and non-smoking related cancers, pointing towards a universal
cancer program. This research gets us closer to understanding the very first
steps in carcinogenesis and in future may provide us with much-needed tests for
risk prediction and early detection.”
- See more at: http://www.ucl.ac.uk/news/news-articles/0515/140515-smoking-cancer-cheek-swabs#sthash.0UH8a0FF.dpuf