The agony of quitting smoking is all too familiar: a repeated cycle of determination and then dwindling resolve, peppered with trials of nicotine gum, patches, and even medication. Some people find success with drugs, such as bupropion (trade name Zyban), an antidepressant commonly prescribed for smoking cessation. But for others, counseling and other strategies seem much more useful than medication.
New research suggests that genetic testing could quickly distinguish which smokers would benefit from bupropion. The findings add to a growing number of studies linking genetics to nicotine addiction and the ability to quit, and raise the possibility that quitting strategies could be more effectively tailored to individual patients.
“It takes a lot for a smoker to prepare themselves to quit smoking,” says Rachel Tyndale, a scientist at the University of Toronto and one of the authors of the new pharmacogenetics study. “If we could identify the right approach in that time, I think it would improve quit rates.”
Bupropion–one of only two non-nicotine smoking-cessation drugs approved by the U.S. Food and Drug Administration–inhibits the rewarding effects of smoking. The drug is broken down by an enzyme called CYP2B6I, whose structure and function vary from individual to individual. In the new study, published this month in the journal Biological Psychiatry, scientists developed a genetic test to identify which of two variations of the enzyme an individual carried–either CYP2B6*6 or CYP2B6*1. They found that people with the CYP2B6*1 variation (about 55 percent of people of European descent) showed no added benefit in quitting smoking when given bupropion: about 30 percent of smokers quit regardless of whether they took the drug or a placebo. Most of the people in this group who successfully quit at the start of treatment were still not smoking six months later.
People with one or two copies of the CYP2B6*6 mutation had a harder time quitting smoking. (In fact, none of the people with two copies of the mutation–one from their mother and one from their father–could quit on placebo.) But this group also showed greater benefit from bupropion: those taking the drug were three times more likely to have stayed off cigarettes at six months than were those taking placebo.
“This is exactly what is needed in the clinical realm,” says Joni Rutter, a program director at the National Institute of Drug Abuse, in Bethesda, MD, which partly funded the study. She points out that in the general population, 80 to 90 percent of those who try to quit relapse within six months. “If we can figure out who will benefit from bupropion before we give it to them, it takes some of the guesswork out of treating the smoking population.”
Such testing could become even more valuable as new smoking-cessation drugs are developed. Varenicline, a new smoking-cessation drug that works via a different mechanism than bupropion, went on the market last year. “Ideally, we would like to be able to say, ‘If you have these variants, you’ll do better on bupropion, but if you have these variants, you’ll do better on varenicline,’” says Rutter.
No gene tests are commercially available for smoking cessation, and scientists caution that individual findings must be replicated before such tests move into standard use. (The current study focused on smokers of European descent, so additional studies are needed to find out if the variation has a similar effect in those of African and Asian descent.)
Not everyone is sure that such tests would help smokers more than existing strategies, such as public-service announcements and government-sponsored booklets on quitting. “We need to develop ways to compare it to existing public-health measures,” says Chris Carlsten, a scientist and pulmonary specialist at the University of British Columbia, in Vancouver. “Intuitively, it’s reasonable to have some doubt that these new approaches can trump the power of the existing, proven, broad-based health approaches.”
If gene tests for smoking cessation do prove useful, they are likelyto come up against some of the issues that have plagued personalized medicine in general: uncertainty over willingness on the part of doctors to prescribe the tests and on the part of smokers to take them, says Nancy Rigotti, thedirector of the Tobacco Research and Treatment Center at Massachusetts General Hospital (MGH), in Boston.
Doctors say that they are less likely to prescribe genomics tests than other tests to patients interested in quitting smoking, according to surveys conducted by Alexandra Shields, the director of the Harvard / MGH Center on Genomics, Vulnerable Populations and Health Disparities. Shields has just finished a new study surveying smokers in rural Alabama and inner-city Baltimore that suggests that they are apprehensive about undergoing genetic testing to help doctors tailor smoking-cessation treatments. “They don’t understand genetics and are fearful of what it might mean for them and their family,” says Shields. “But if we can make the resources available to educate physicians and patients, then I think the potential to increase the quit rate and reduce the public-health burden of smoking is substantial.”
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