Damage Patrol: Enzyme may reveal cancer susceptibility

Breaks in a person’s DNA underlie the cancer-causing effects of cigarette smoke. Such DNA damage can lead to mutations that bring about the aberrant cell growth of cancer. But since not all smokers get lung cancer, scientists have assumed that some people mend their damaged DNA strands better than others do. With this in mind, researchers have been searching for enzymes that orchestrate DNA repair and mitigate cancer risk.

Now, scientists report that people with lung cancer are shortchanged when it comes to at least one type of DNA repair. Such patients show less activity of a repair enzyme called 8-oxoguanine DNA N-glycosylase (OGG) than people without the disease do, researchers say in the Sept. 3 Journal of the National Cancer Institute. The enzyme fixes DNA that’s been damaged by oxidation.

“We think testing for OGG activity will provide a useful tool for lung cancer prevention,” says study coauthor Zvi Livneh, a biochemist at the Weizmann Institute of Science in Rehovot, Israel.

For their study, Livneh and his colleagues recruited 136 people, half with lung cancer and half without any cancer. Tests of OGG activity in the volunteers’ blood samples indicated that while only 4 percent of people free of cancer were significantly short on OGG activity, 41 percent of the cancer patients were.

Both groups included smokers and people who had never smoked. Smoking didn’t affect OGG activity in either group, the researchers found. Moreover, the tumors in the cancer patients didn’t appear to be responsible for their lower OGG activity, says Livneh, because blood tests before and after surgery to remove tumors revealed no change in participants’ OGG activity.

To ascertain whether OGG activity changes over time, the researchers drew blood samples over 3 years from eight of the healthy nonsmokers. The OGG scores of each of these volunteers remained stable.

Smoking boosts a person’s lung cancer risk 10-to-20-fold. The Israeli researchers calculate that smoking and having low OGG could together increase an individual’s risk of lung cancer to more than 100 times that of someone who has never smoked and has average OGG activity.

Screening smokers for low OGG activity could pinpoint individuals at especially high risk for lung cancer, Livneh says. “These smokers, we believe, will have a stronger motivation to quit because they have a personal susceptibility,” he adds.

Before OGG screening is ready for the clinic, however, more testing is needed, says Neil Caporaso, an epidemiologist at the National Cancer Institute in Bethesda, Md. Future OGG studies will need to assess participants’ intake of antioxidants, such as vitamins C and E and the fruits and vegetables that contain them, he says. He also recommends that researchers note each study participant’s smoking behavior–heavy or light, current or former–to get a better idea of the DNA-repair task that’s confronting him or her.

“Large-scale work in human populations will be required to confirm effects in realistic settings and to gauge public health implications,” says Caporaso. “The investment should be worth it.”

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