Cigarette smoke contains nearly 4,000 chemicals, some of them highly carcinogenic, and so doctors have long known that smoking greatly increases the risk of lung cancer. In fact, nearly 90 percent of all lung cancer cases are caused by cigarettes.

What scientists don’t know, however, is why only 1 in 10 smokers—and not a much higher percentage—actually develop the disease.

A new study headed up by Penn researchers Ian Blair and Trevor Penning aims to answer that question—and, hopefully, find the genetic reasoning for why some people develop cancer and others don’t. If they’re successful, Blair and Penning believe, doctors and public health officials could soon have a new weapon in the battle against lung cancer.

“We are trying to figure out who is likely to develop cancer and who’s not,” said Penning, director of Penn’s Center of Excellence in Environmental Toxicology. “You can say, simply, that people shouldn’t smoke, and they shouldn’t. But despite our best efforts, we’re not very successful at that. People are just not quitting.”

For the study, Penning and Blair will screen smokers, non-smokers and individuals who are regularly exposed to second-hand smoke in an attempt to find the biochemical “markers” that might indicate a susceptibility to cancer. Other studies have shown that exposure to cigarette smoke causes chemical changes within the body, but until now, there has been no large-scale effort to accurately identify exactly which of those changes are indicators of cancer.

Blair and Penning hope they can zero in on exactly which biomarkers are found in people who have developed cancer, but are not found in those who don’t get the disease. The project will be supported by a $2.3 million grant from the National Institute of Health’s Genes, Environment and Health Initiative (GEUI).

The researchers say the study represents an important step forward, and a new prevention model, in the fight against lung cancer. Until now, public health officials have focused on smoking prevention programs, but those programs haven’t exactly taken hold: According to the American Heart Association, more than 45 million Americans are smokers.

If Blair and Penning are successful in identifying the specific biomarkers that indicate cancer risk, however, they could help researchers develop a sort of lung cancer “test.” Just like cholesterol tests serve as wake-up calls for people at risk for heart disease, this lung cancer test could finally help doctors pinpoint those individuals who are on the cusp of developing cancer. Maybe more to the point, this test could scare smokers into quitting.

“It’s one thing to slap a warning label on a pack of cigarettes,” said Blair, vice chair of the Department of Pharmacology. “But if were able to show people something like, ‘This is what your DNA looks like, and it’s because you smoke,’ maybe that would convince them to stop smoking.”

The NIH is watching the Penn study closely, Blair said, and for good reason: If it is a success, other similar projects may get funding as well.
“This study has put us right where the action is,” Blair said.

Originally published Oct. 4, 2007.