Genes May Make It Harder for Some to Quit Smoking

If you're a smoker, kicking the habit is one of the best things you can do for your health. Smoking leads to many dangerous health conditions and is the No.1 cause of deadly lung cancer.

It's never too late to quit. Just 20 minutes after you do, you're body starts to heal itself. Your blood pressure drops and your heart works better. Those who quit and stick with it for 10 years cut their risk of lung cancer death in half.

Yet, quitting can be tough and may take more than one try. Giving up tobacco can trigger withdrawal symptoms such as anxiety, irritability, hunger, and problems concentrating.

Adam Leventhal PhD  "These unpleasant symptoms can make you want to go back to smoking," says Adam Leventhal, PhD, associate professor of preventive medicine and psychology at the USC Norris Comprehensive Cancer Center. "But what's interesting is some people have really severe withdrawal symptoms but others don't."

Your genes may have something to do with how hard or easy it is to quit. Leventhal is now conducting an American Cancer Society-funded study to examine the genetics of certain smokers and determine why some have more severe withdrawal symptoms than others. He hopes his findings could help lead to a more personalized approach to smoking cessation planning.

Focusing on High-Risk Smoking Population

Leventhal's research is currently focusing on African American smokers. They are more likely to die from lung cancer than Caucasians, even though they smoke about the same amount or maybe even less. Access to health care and seeking treatment after diagnosis may play a role, however the specific reasons for the disproportionate burden aren't clear. Some research also suggests blacks who smoke a pack a year generally inhale more smoke than whites. "It may be the culture of how one smokes and not necessarily race-based genetics that leads to blacks getting cancer with fewer packs," says American Cancer Society Chief Medical Officer Otis Brawley, MD.

Regardless, quitting should be an important priority. But, “there’s some evidence that when [African Americans] try to quit, they are less successful," Leventhal says. "We need to have a better understanding of the biology of tobacco addiction, particularly in this high-priority population." To do this, his team is collecting saliva or blood samples from hundreds of African American men and women who smoke, with an average age in their 40s. The sample is sent to a DNA center for a one-time genetic analysis. The study participants come back to Leventhal's laboratory at two different times: Once after they have been smoking as usual and the second time after they've abstained from smoking overnight (or, for about 16 hours).

"We can verify biologically that they didn't really smoke, so we know they're in an active state of withdrawal," explains Leventhal. "So we can get a really accurate measure of how their state changes from when they are smoking to when they're not."

At both visits, the participants are asked a series of questions relating to how they feel at that moment. For example, "Are you craving a cigarette right now?" or "Are you having any anxiety?" They're also given an opportunity to earn money while avoiding the urge to light up during their 50-minute study visit. For each 5 minutes that they delay smoking, they earn a small reward.

"We are trying to model what happens when people lapse," says Leventhal."What you see in this case is when people haven't smoked, they will smoke much sooner. They are willing to forgo the chance to get the money in order to smoke, whereas those who smoked recently can last much longer."

Scientists are comparing the questionnaires and reward task outcomes for each participant and note any behavioral and withdrawal changes. They are now creating a "change score" for each person to see how much abstinence affects them. The next step is to link these scores to each person's genetic profile to see which, if any, genes may predict who is at higher risk for withdrawal.

"We have some suspect genes, but no one has really studied withdrawal very well. With this award from the American Cancer Society, we are able to do the best study to date on withdrawal," says Leventhal.

Is Pain a Withdrawal Symptom?

Leventhal is only about a third of the way through his research project. His team has collected samples from about 250 people so far and they are currently working to analyze the results. Early evaluations reveal that pain may be a potential tobacco withdrawal symptom.

"Our smokers, on average, report that they have more physical pain on the abstinent day versus when they smoke," he says, adding that the finding particularly occurs in people who reported chronic pain issues, like back pain. He says it could be psychological, but there's also some research that shows nicotine supplies the brain's opioid pain system.

"Doctors should know that when trying to advise a patient with chronic pain to stop smoking, that doing so may cause their pain to flare up," Leventhal says. He suggests that doctors discuss additional interventions to address that. "It could interfere with their pain disorder and cause them to relapse and start smoking again."

Improving Smoking Cessation Therapies

Revealing if specific genes are involved in tobacco withdrawal could have a significant impact on a smoker's ability to successfully stop smoking and remain tobacco free. Leventhal envisions medications that one day target the specific biological events involved in the feeling of withdrawal symptoms.

"If we can help contribute to the development of a novel medication that helps people quit and is better than what's out there, or works for a different subgroup of a particular population, then it will have a massive impact on the lung cancer burden," he says.

His genetic profiling research could also lead to personalized smoking cessation plans, since it may ultimately help predict who may or may not have a hard time kicking the habit.

"In the future, your doctor could look at your gene profile and say 'You're at very high risk for withdrawal syndrome, so let's start talking about coping strategies or discuss using a medication that could help with that.'" says Leventhal.

The bottom line: It might be harder for others to quit smoking. Experts say even if genes may play a role, you should still try. Genes may have an impact, but culture experiences and personal behaviors certainly play a role. Saying goodbye to tobacco can make a significant impact on your health now, and in the future.

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