Scientists at the Weizmann Institute have discovered a new genetic risk factor that increases the susceptibility of smokers to lung cancer. Published in the Journal of the National Cancer Institute, the findings show that smokers who carry the newly discovered genetic marker are around 120 times more likely to get lung cancer than non-smokers who do not have the risk factor. A simple blood test based on these findings will be able to detect smokers who are at especially high risk of developing lung cancer.
The findings, made by Prof. Zvi Livneh and Dr. Tamar Paz-Elizur of the Biological Chemistry Department, are a result of many years of research conducted on the role of DNA-repair mechanisms in cancer. The scientists focused on lung cancer, one of the most common and most deadly cancers, responsible for 30 percent of all cancer deaths. In the USA alone there are 160,000 new patients per year. Smoking is the major cause of lung cancer, and 90 percent of hospitalized lung cancer patients are smokers. However, only 10 percent of heavy smokers develop the disease, suggesting involvement of a personal genetic susceptibility. Livneh struck up a collaboration with Dr. Meir Krupsky of the Chaim Sheba Medical Center to determine whether this susceptibility is caused by a decreased ability to repair DNA damage.
Our DNA is damaged about 20,000 times a day by factors such as sunlight, smoke and reactions within the body. If left unrepaired, damages to the DNA can lead to cancer. Fortunately the body has a stock of enzymes whose function is to repair DNA. These enzymes scan the DNA and detect damage using sophisticated sensor systems. Upon detection of damage, the enzymes perform an 'operation' on the DNA, cutting out the damaged part and replacing it with a new DNA part. Thus the efficiency of the repair systems is critical for the prevention of cancer.
Livneh and his team concentrated on a specific DNA repair enzyme, called OGG1 (8-oxoguanine DNA glycosylase 1). This repair enzyme deletes DNA parts damaged by toxic molecules called oxygen radicals, which are found in tobacco smoke. The team developed a new blood test that enabled them to measure the level of activity of OGG1. Using this method, the researchers found that 40 percent of lung cancer patients have low levels of OGG1 activity, in contrast to only 4 percent of the general population.
These and other findings published in the study show that low OGG1 activity results in high susceptibility to cancer: 5-10 times more than those whose OGG1 activity is normal. Smoking increases this risk, since it causes more damage for DNA repair enzymes, including OGG1, to fix.
Smokers who have a low level of OGG1 activity were found to have the greatest risk of lung cancer, as much as 120 higher than non-smokers with regular levels of OGG1 activity. These findings suggest that a substantial portion of lung cancer cases might result from a combination of smoking and reduced OGG1 activity. If so, then screening smokers for low OGG1 activity will help them make more informed decisions to stop smoking. Of course, even smokers with normal OGG1 activity are at a greater risk of getting lung cancer than the general population and the blood test will not ensure that they don't get the disease. In addition, smoking causes other types of cancer and cardiovascular diseases, whose relation to OGG1 activity is still unknown.
The Weizmann team also included Dr. Sara Blumenstein and Dalia Elinger. Statistical analysis was conducted by Dr. Edna Schechtman from Ben-Gurion University.
Prof. Zvi Livneh's research is supported by the Dolfi and Lola Ebner Center for Biomedical Research, the Levine Institute of Applied Science and the M.D. Moross Institute for Cancer Research.
Prof. Livneh is the incumbent of the Maxwell Ellis Professorial Chair in Biomedical Research.
More information can be found at Prof. Livneh's website:
Message posted by: Frank S. Zollmann
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