Got good enzymes? How well smokers' cells clear DNA damage may impact their lung cancer risk.

Undoing the Smoke Damage

Although smoking has long been linked to lung cancer, only 10% of heavy smokers develop the disease. Why them? One factor may be the activity of DNA repair enzymes, which can undo some of the damage caused by smoking. A new study finds that smokers with an underperforming repair enzyme are much more likely to get lung cancer.

About 150,000 people die from lung cancer each year in the United States. Many cases can be traced back to smoking, which causes DNA in lung cells to mutate at a high rate. Because enzymes can fix this kind of damage, DNA repair scientist Zvi Livneh of the Weizmann Institute of Science in Rehovot, Israel, and his colleagues wondered whether the enzymes might be faulty in smokers who develop lung cancer.

To find out, Livneh's team looked for a common DNA repair enzyme, called OGG1, in the blood of 68 patients with non-small-cell lung cancer and 68 healthy individuals; both groups included smokers and nonsmokers. The researchers extracted OGG1 from the blood samples and added it to DNA they had synthesized in the lab. The DNA samples carried the kind of damage that smoking causes.

OGG1 was less active than normal in 41% of cancer patients and 4% of healthy participants, they report in the 3 September Journal of the National Cancer Institute. Smokers with sluggish OGG1 were up to 10 times more likely to have lung cancer than those whose enzyme worked normally and 120 times more likely than nonsmokers with normal enzyme activity. Nonsmokers with bad OGG1 were up to 10 times more likely to have cancer. This suggests that reduced OGG1 activity could be a risk factor for lung cancer in the general population--not just among smokers.

The findings are "novel" and "significant," says Samuel Wilson, a biochemist at the National Institute of Environmental Health Sciences. He adds that if the findings hold up, they could lead to earlier detection and prevention of lung cancer.

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Zvi Livneh
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