Smoking induces early signs of cancer in cheek swabs

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, Head of the Department of Women's Cancer at the 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.

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.