Smokers' Windpipes Could Hold Clue to Lung Cancer

(April 8) -- A simple genetic change inside the windpipes of smokers could help doctors determine who's at risk of developing lung cancer, or diagnose the disease early enough to offer more effective treatment.

The discovery, published in this week's ScienceTranslational Medicine, indicates a key shift in lung cancer research, focusing on the entire respiratory tract of smokers rather than merely the lungs.

Genes turn on and off as the body tries to ward off cellular damage from smoking. Researchers at the Boston University School of Medicine, led by Dr. Avrum Spira, wanted to see if they could track those changes and identify a genetic pathway that might indicate increased risk of lung cancer.

Since cigarette smoke bathes the entire respiratory tract, from tongue to lungs, the team decided to start at the top. Using data from two separate studies on current and former smokers, the researchers discovered that a genetic pathway -- PI3K -- is activated in the windpipes of those with precancerous lesions.

"These cells are like a canary in the coal mine," Spira told Reuters. "Even though lung cancer develops deep down in your lungs when you smoke, these cells can tell you whether you are on the way to developing lung cancer. It is sort of a window into the lung."

What they don't know is whether this group of genes accounts for all cases of lung cancer. That means smoking isn't safe for anyone, even current smokers who don't have an active PI3K pathway, because other genes could be implicated in the disease.

But a test based on PI3K could help detect lung cancer earlier. Most diagnoses occur too late to mitigate the illness, which is the most common killer of all cancers and afflicts 10 to 20 percent of smokers.

Such a test would also be useful in detecting risk in former smokers, who still face increased vulnerability to lung cancer despite kicking the habit. Those whose genetic signature has changed could be monitored more closely.

"Even for people who have stopped smoking, there's a significant risk of cancer down the road, and it would be nice to identify which patients are really at risk," Dr. Neal Ready, a lung cancer specialist at Duke University, told The Associated Press. "To have some sort of molecular test that would identify those patients would be very useful."

And if the PI3K pathway could be turned off, the discovery might also lead to a new method of preliminary lung cancer treatment.

The American Cancer Society is cautiously optimistic about the finding, but Dr. Michael Thun, the organization's vice president of epidemiology, wants to see more evidence.

"It's an interesting and potentially important finding, but it's still a long way from being clear what its clinical application will end up being. These things need to be replicated," he told The Boston Globe. "It is far from the total picture of the heterogeneity of lung cancer."

Spira and other researchers have immediate plans to bolster their findings. They'll create a test based on the genetic signature and begin a clinical trial of nearly 800 current or former smokers.