Video: New test IDs smokers prone to lung cancer

  1. Transcript of: New test IDs smokers prone to lung cancer

    BRIAN WILLIAMS, anchor: It has always been a medical mystery. You take two heavy smokers, one of them gets lung cancer , the other doesn't. Why is that? There is a new clue along those lines tonight and, if researchers are right, there may also be a relatively easy way to reduce the risk. More on this story from our chief science correspondent Robert Bazell .

    SUE: Hi, Loretta.

    Ms. LORETTA ROCHE: Hi, Sue.

    ROBERT BAZELL reporting: Loretta Roche is one of 90 million Americans who once smoked cigarettes or still do.

    Ms. ROCHE: Yeah, it was the thing to do.

    BAZELL: Despite the enormous risk, only 10 to 20 percent of current and former smokers develop lung cancer . And Roche is part of a study that seems to explain why.

    Dr. AVRUM SPIRA (Boston University School of Medicine): There are significant alterations.

    BAZELL: Dr. Avrum Spira and his team have identified a set of genes shown in this pattern on a computer chip .

    Dr. SPIRA: And we specifically found that this high level of activity of these genes precedes the development of lung cancer . So they're on their way to getting lung cancer .

    BAZELL: Before the cancer develops, people with this gene pattern usually get dysplasia, abnormal cells that often become cancer .

    Dr. SPIRA: And we can actually reverse the activity using a drug that inhibits this pathway.

    BAZELL: The drug is called inositol, a plant product with few side effects already sold in health food stores. In a small initial experiment, Dr. Spira found that in six of 10 people the drug returned the gene pattern to normal and their abnormal cells also appeared healthy again. The National Cancer Institute already is testing inositol in former smokers to see if it reduces the rate of lung cancer .

    Dr. SPIRA: Those gene activity patterns can tell us something about...

    BAZELL: But this latest research shows the treatment could be more targeted.

    Dr. SPIRA: Here we go, OK?

    BAZELL: For now the cells for testing can only be recovered with a bronchoscope that goes deep in the airway. But the researchers believe they soon will be able to test cells from the nose or throat. What would you think if somebody took your work to be an excuse to continue smoking?

    Dr. SPIRA: Well, I think that would be a mistake . Lung cancer is only one of many diseases that are associated with cigarette smoke exposure.

    BAZELL: Still , this early work holds the promise of reducing deaths for what, Brian , is still the biggest cancer killer.

    WILLIAMS: Now this is along the lines of the question you just asked that doctor. People with a heavy smoker in the family, someone who's just decided they can't quit, if they called having seen this story and said start taking this stuff, would that be wrong? Would that be bad?

    BAZELL: I don't think it would be wrong or bad. And they can certainly do it. It's for sale in health food stores. Now, no responsible doctor is going to advise them to do it because there's a clinical trial .

    WILLIAMS: Right.

    BAZELL: And until that's finished, we don't know if it's going to work and we don't know if some untoward side effect that we haven't anticipated is going to appear.

    WILLIAMS: Part of this era of multiple uses for things with one intent. Bob Bazell , thanks for stopping by, as always.

By AP Medical Writer
updated 4/7/2010 7:38:39 PM ET 2010-04-07T23:38:39

Scientists may have found a way to tell which smokers are at highest risk of developing lung cancer: measuring a telltale genetic change inside their windpipes.

A test based on the research is being developed in hopes of detecting this deadly cancer earlier, when it's more treatable.

And if the work pans out, the next big question is: Might it even be possible to reverse this genetic chain reaction before it ends in full-blown cancer? The researchers found a tantalizing early hint among a handful of people given an experimental drug.

"They're heading toward lung cancer, and we can identify them with this genomic test," said Dr. Avrum Spira of Boston University School of Medicine, who led the research published Wednesday in the journal Science Translational Medicine.

Leading cancer killer
Lung cancer — which killed nearly 160,000 Americans last year — is the leading cancer killer, and cigarette smoke is by far its main cause. Yet only a fraction of smokers develop lung cancer, and there's no way to predict who will escape it and who will not. Nor is there a good way to detect early-stage tumors. Consequently, most people are diagnosed too late for today's treatments to do much good. Learn more about lung cancer

"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," said Duke University lung cancer specialist Dr. Neal Ready, who wasn't involved in the new research but called it intriguing.

"To have some sort of molecular test that would identify those patients would be very useful," he added, because they could receive close monitoring with lung scans that aren't practical for everybody.

Rather than focusing on the lung itself, Spira's team took a different approach. Smoking bathes the entire respiratory tract in toxins. So he hunted for the earliest signs of impending lung cancer upstream, in how different genes are turned on and off inside the upper airway as the body tries to defend itself and those defenses weaken over time.

At least 100,000 smokers or former smokers a year have a tube snaked down their throat to look for signs of cancer if an X-ray or other test detects something suspicious, Spira explained. Bronchoscopies can be used for a look down into the lung, but Spira was interested instead in cells that line the windpipe, collected during the same procedure.

Video: Doctor discusses test's impact Sure enough, he found a genomic signature — a pattern of gene activity — in otherwise normal windpipes that distinguished some current or former smokers who had lung cancer from those who didn't.

Then with Dr. Andrea Bild of the University of Utah, Spira analyzed cells from 129 current and former smokers and found the genes involved were part of a well-known cancer-causing pathway named the PI3K pathway. When PI3K-related genes are too active, too much cell growth can occur, but most studies have examined those genes only in tumors.

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On Wednesday, Spira reported finding PI3K activation in some current or former smokers with precancerous lesions, too, but not in those with other lung diseases.

Spira cannot estimate how much lung cancer might come from this genetic pathway. Nor does the work mean it's OK for people without this marker to keep puffing. Other lung cancer pathways could be at work, and smoking also causes heart attacks, other lung diseases and other cancers.

But a company Spira helped found, Allegro Diagnostics Inc., is beginning a study of up to 800 current and former smokers who need a bronchoscopy anyway to see how well a test based on the research performs.

Moreover, there are some experimental drugs being designed to fight PI3K activation. One compound already had been tested in nine smokers with precancerous lesions, six of whom had their lesions improve. Spira's team went back and checked those study participants' previously stored airway cells — and found those who had responded to the compound indeed had their PI3K activity drop, a preliminary but exciting clue in the quest to develop cancer-preventing drugs.

"There's enough evidence in this article to start down that road" of researching PI3K chemoprevention, said Duke's Ready.

Copyright 2010 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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