Risk of lung cancer measurable from DNA damage

Copenhagen: The risk of smokers of developing lung cancer can now be measured far more accurately than before. According to research from the University of Copenhagen, DNA damage can reveal the risk of lung cancer. Hopefully, this discovery can reduce the number of lung cancer-related deaths. Tobacco smoking causes illness and disability and globally causes 12 per cent of all premature deaths. In collaboration with a group from Bristol University, UK, a research team from the Faculty of Health and Medical Sciences at the University of Copenhagen has discovered that a particular epigenetic change is a very precise marker for the risk of developing lung cancer. The change in question is DNA methylation, a biochemical process which, among other things, switches genes on and off. The lower the level of methylation, the higher the risk of lung cancer. The discovery can help reduce the mortality rate for lung cancer, explains Stig Bojesen, professor and consultant doctor at the Department of Clinical Biochemistry at Herlev and Gentofte Hospital.

“We can use a blood sample to identify the level of methylation in the patient’s DNA. This enables us to offer a more precise estimate of the patient’s risk of developing lung cancer than is possible with the current methods. We will therefore be able to target lung cancer screening towards (former) smokers who actually are in the high-risk segment,” says Stig Bojesen.
The researchers reviewed data from more than 9,000 persons who participated in a Danish general population study, the Østerbro study, in the early 1990s. By studying the DNA in blood samples taken back then, the researchers are able to measure the participants’ level of methylation at the time and compare them to see if any participants subsequently developed lung cancer. The results show that there is a close correlation between a low methylation level and a high risk of developing lung cancer.
New method much more accurate
Smoking creates a sort of scarring in the DNA, which takes many years to heal after you stop smoking. Smoking behaviour is currently mapped by measuring the cotinine level in the body. Cotinine is a decomposition product of nicotine. The problem with measuring cotinine is that it can only be measured up to a few days after smoking, so it is not applicable, for example, for saying anything about previous smoking habits and thus the lung cancer risk of ex-smokers. Therefore, persons being screened in the United States are additionally asked to fill in questionnaires about their smoking habits, but this method is also insufficient, Stig Bojesen believes.
“People tend to understate their own smoking habits, because they know that smoking is unhealthy. It is also difficult to list the many details required for us to be able to predict risk. This may be the number of drags that people on average have made from a cigarette throughout their life, how long the smoke was in their lungs etc. Measuring the level of methylation in the DNA from white blood cells is far more accurate and objective than the information people themselves are able to provide about their smoking habits,” he concludes.