Using Genetics to Prevent Lung Cancer

Genetic information is often used to guide precision cancer treatments. In the future, genetics could guide personalized efforts to stop smoking and prevent lung cancer.

343,000+. That’s the number of cigarettes Chris Kneibert, 65, has probably smoked over his lifetime.

“I basically smoked a pack a day for 47 years,” he said. “And there are 20 cigarettes in a pack. I smoked when I woke up or when I got bored. I smoked in the mornings and socially. It seemed like the thing to do when I first went to college, and I never really stopped — or couldn’t.”

The Centers for Disease Control and Prevention estimates that 49.2 million people in the U.S. — one in five adults — use tobacco products. Add e-cigarettes/vaping, cigars and smokeless tobacco products, and the number rises. With today’s average cost of cigarettes at more than $8 per pack, that means Kneibert and other smokers dole out almost $3,000 annually to support a pack-a-day habit.

The bigger problem comes when individuals want to quit smoking. Tobacco products contain nicotine, a known addictive chemical. When people smoke, the nicotine absorbs into the bloodstream and increases dopamine levels in the brain. Smokers then start craving the “hit” of nicotine, ingesting it more and more, and rapidly become addicted. Trying to quit causes withdrawal symptoms, and about half the people who want to quit, can’t.

“I really thought I could quit on my own, but I enjoyed it too much,” said Kneibert. “Even when news came out that smoking was bad for you and could cause cancer or heart attacks and stroke, I didn’t stop. It really was an opportunity for me to step outside and smoke a cigarette and temporarily get out of whatever I was doing.”

In the 1980s, the U.S. Food and Drug Administration (FDA) approved a nicotine gum, Nicorette, as the first medication to help people quit. Over-the-counter sales of Nicorette were authorized in 1996. Along the way, a plethora of other treatments became available, including hypnosis and behavioral therapy as well as phone and web-based counseling services to support those who wanted to quit. Still, many people can’t stop smoking.

“I tried the nicotine gum and was successful for only one to two months, said Kneibert. “I was not optimistic I could succeed and stop smoking.”

Using Genetics to Quit Smoking

Last year, Kneibert was told about a new clinical trial underway at Washington University School of Medicine in St. Louis. The study focuses on gathering genetic information from individuals identified as smokers to better understand the mechanisms behind their smoking addiction as a tool for identifying optimal treatment options.

“I am very interested in how we can motivate people to have healthy behaviors,” said Washington University psychiatrist and physician scientist Li-Shiun Chen, MD, MPH, ScD, director of the Tobacco Treatment Program at Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine. “Precision medicine is used in cancer treatment but not used in cancer prevention. We wanted to know if we could use precision medicine to affect behavior and lower the risk of health problems stemming from smoking. We, therefore, could shift the paradigm from cancer treatment to potentially cancer prevention using genetics and targeted therapies.”

Two years ago, Chen, along with organizational psychologist Alex Ramsey, PhD, and their colleagues in Washington University’s Precision Prevention and Treatment Lab received grants from the National Institutes of Health to see if individualized counseling along with a personalized genetics report highlighting the percentage of cancer risk would result in more effective treatment and smoking cessation rates. The first trial, PRECISE, focused on identifying the level of risk for lung cancer and counseling on the benefits of lung cancer screening for each study participant. In the second trial, MOTIVATE, researchers added information related to genetic markers that identified optimal smoking cessation treatments for each participant.

“Like an ACT test for college, a genetics ‘score’ can tell you your own individual lung cancer risk and, significantly, how difficult it may be to actually quit smoking,” Chen said. “We analyzed DNA and created a report that not only showed the benefits of quitting smoking but, significantly, also showed which smoking cessation products might be better for a person to try based upon their own genetic profile.”

In the MOTIVATE trial, the team analyzed more than 50,000 biomarkers linked to elevated cancer risk in 100 study participants. A report then was shared with both primary care physicians and patients to see if it would motivate individuals to stop smoking.

The report identified genetic markers and noted whether a person had a high or low nicotine metabolism level. “If you have a slow metabolism, you could use an other-the-counter nicotine patch to help you quit,” Chen explained. “But if you have a fast metabolism, nicotine patches or gum are less likely to work. In those cases, individuals would be more successful if they used a prescription medication.”

See an example of a personalized report here.

For Kneibert, an early participant in the MOTIVATE trial, he had a genetic marker that pointed toward a fast metabolism. His report also showed that he had a very high risk for developing lung cancer. “It was in the red zone, which was bad,” he recalled. He agreed to try Varenicline, one of seven FDA-approved prescription medications to help adults quit smoking. To his surprise, it worked.

“I started with one pill a day and still smoked,” he said. “But when I got to two pills a day, the medicine stopped my nicotine receptors from working. I would smoke and think to myself, ‘That was very unappealing.’ I quit about a month later and I’ve been smoke-free ever since.”

Chen and her colleagues still have a long way to go before they say their research will make a huge impact in the field of cancer prevention. The MOTIVATE trial is still underway, and they plan to recruit 800 participants to continue testing whether the genetics report motivates people to change behavior, stop smoking and get regular screenings for lung cancer. Still, publication last year of their early research is gaining attention.

“I believe we are at the forefront of innovation, and Siteman Cancer Center is really leading the country by using genetics for cancer prevention,” stressed Chen. “Patients and their doctors are more motivated when we can offer evidence-based risk assessments and smoking cessation treatment suggestions. I predict that we can move the needle on effective addiction treatment and, therefore, prevent some cancers because of our work.”

Kneibert now steps outside often to enjoy nature instead of smoking a cigarette. He also got a lung cancer screening, testing negative for any cancer. “I’m glad I found out why the nicotine patch didn’t work before,” he said. “That report was eye-opening and made me want to try to quit again because it really wasn’t my lack of willpower that caused me to fail.”

“I’m proud of myself for quitting,” he added. “And my kids are proud of me, too.”

To learn more about the MOTIVATE trial call 314-273-3826.

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Chen, Tony et al. Genomic insights for personalised care in lung cancer and smoking cessation: motivating at-risk individuals toward evidence-based health practices. eBioMedicine. December 2024.