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A new study suggests a link between genes and addiction to nicotine. Following is a press release issued by ASH, followed by excerpts from several articles.

ASH PRESS RELEASE:

GENE STUDY IS ONLY FIRST STEP TOWARD NICOTINE ADDICTION CURE

DON'T WAIT TO QUIT, DON'T BLAME YOUR GENES, AND DON'T START, SAY EXPERTS

A study showing that genetics may contribute to nicotine addiction is only a tiny first step towards a possible treatment; one which may still be far away even if the initial research is verified by others.

In the meantime, don't use "my genes make me do it" as an excuse to attempt quitting using existing methods; don't put off trying to quit because it may be easier if a therapy is developed; and don't start if you aren't a smoker, suggests Action on Smoking and Health (ASH), a national antismoking group.

"If you don't start, you will never become addicted to nicotine," says John Banzhaf, Executive Director of ASH, noting that no one can tell if they or their children are in the small percentage of the population in which genetic disposition may offer some protection against nicotine addiction.

Moreover, even for those who are already addicted, there are enormous health benefits to quitting now, and not waiting for some possible new treatment based upon the gene study. "Of those who choose to wait, many will die, and other will suffer debilitating conditions like emphysema," he says.

"Being addicted doesn't mean you can't quit; millions of people who were addicted to nicotine, alcohol, and heroin have managed to stop."

Being addicted only means that it is more difficult than breaking a habit because your body exhibits withdrawal symptoms, not that it is impossible.

Indeed, notes Banzhaf, breaking the addiction has become less difficult recently because of the availability of nicotine gum, patches, and other methodologies of administering the drug in smaller slower-acting doses which reduce the problems of withdrawal without necessarily reinforcing the addiction.

Although it has been estimated that as many as 80% of all smokers become addicted to nicotine, many millions have quit over the years despite the pharmacological hold the drug can have. "This new study may suggest that there is some light at the end of the long tunnel of addiction, but smokers must be careful not to be killed in the tunnel while waiting for that light," says Banzhaf.

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Excerpts from CIGARETTE ADDICTION PROBED BY SCIENTISTS

Medical Industry Today [06/25/98]

Scientists are gaining more insight into the differences among people relating to issues that have received much attention lately--cigarette addiction and tobacco-related cancers.

The scientific community has discovered why certain individuals never become addicted to cigarettes, and why all smokers do not develop tobacco-related cancers.

For some people, a common genetic defect reduces their ability to metabolize nicotine, the addictive ingredient in cigarettes, making them less likely to become smokers, Reuters reported. And if they do take up the habit, they will smoke fewer cigarettes.

In a letter in the scientific journal Nature on Wednesday, researchers from the University of Toronto stated that smokers with a faulty CYP2A6 gene also have increased protection against cancers because their bodies are less efficient in turning the dangerous ingredients in cigarettes into carcinogens that produce cancer, according to the report.

"This is the first gene that has clearly been identified that affects the development of the regular smoking pattern,' Dr. Rachel Tyndale, a pharmacologist at the university, told the news agency.

The CYP2A6 gene produces an enzyme that metabolizes nicotine. If scientists could block the function of the enzyme with a drug, they may be able to prevent and treat people who are addicted to tobacco.

"We're interested therapeutically because we believe we can imitate the genetic defect and use this as a (drug) therapy," Tyndale said.

Individuals addicted to cigarettes must adjust their smoking to maintain constant blood and brain nicotine levels.

A drug that could block metabolism of nicotine could prevent people from becoming addicted to tobacco or could help smokers maintain their nicotine level for longer so that they would need fewer cigarettes, making it easier for them to eventually quit.

Tyndale envisions development of a pill that smokers could take in the morning that would block the enzyme function for upwards of 24 hours, according to the report.

Researchers are testing how smoking behavior can be changed in humans. The next step would involve a pharmaceutical company to commercialize any treatment.

If everything goes well, a drug therapy could be just a few years away, according to Tyndale.

Further down the road, the gene could be a target for gene therapy, the report states.

There are three types of CYP2A6 genes, one normal and two defective.

Everyone has two of the genes, one inherited from each parent. One percent of the population carry two deficient CYP2A6 genes, which gives them the most protection from tobacco. Furthermore, people who have one functioning and one faulty gene also have the defect.

Tyndale and colleagues, Edward Sellers and Michael Pianezza, examined 184 people who had never smoked and 244 people who were addicted. They said that 20 percent of non-smokers carry a defective version of the gene, compared to only 10 percent of smokers.

Among the smokers, those with the faulty gene smoked an average of 129 cigarettes a week compared to 159 a week for people without the defect.

"Even just having one half of the impairment can make a big difference in terms of whether people are likely to become smokers. If we can imitate that, or imitate the people who have no nicotine metabolism, we feel that this would be a really strong therapeutic approach," Tyndale said.

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Excerpts from GENE KEEPS SOME FROM NICOTINE ADDICTION, STUDY SAYS

New York Times [06/25/98]

Scientists say they have identified a gene that helps protect some people from becoming addicted to cigarettes, according to a study. If confirmed, the finding may lead to medications that help smokers cut back or quit.

About one-fifth of the nonsmoking population has a protective version of the gene, said Dr. Rachel F. Tyndale, an author of the study. The gene's influence may have kept some seven million residents of North America from becoming addicted to nicotine, Dr. Tyndale said.

The gene is at least the second thought to affect the risk of becoming addicted to nicotine; genetics experts believe that the basis of addiction is more complex than one or two genes. They warn that the case for the newly discovered gene is far from proved.

Dr. Tyndale and her colleagues at the University of Toronto in Ontario will report their findings in today's issue of the journal Nature.

A nicotine researcher at the University of California at San Francisco, Dr. Neal Benowitz, said the result made sense biologically. But Dr. Benowitz cautioned that in the past, similar early findings of addiction genes had not been confirmed by further research.

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Excerpts from DEFECTIVE GENE MAY HELP SMOKERS QUIT

by Robert Davis, USA Today [06/25/98]

A defective gene that makes smoking unpleasant could be the clue to a cure for nicotine and other addictions, says a study in today's Nature.

The study of 244 nicotine-dependent smokers and 184 people who had tried smoking but never got hooked found the genetic defect was more common in occasional smokers.

At least one bad copy of the gene showed up in 12% of dependent smokers vs. 19% in occasional smokers.

The gene may cause some people to break down nicotine more slowly than others, say researchers at the University of Toronto.

When nicotine stays in the body longer, it is more likely to cause unpleasant side effects like nausea. Researchers think this bad experience keeps some from addiction.

"If you can't break it down, you don't like it a lot," says Alan Leshner, director of the National Institute of Drug Abuse at the National Institutes of Health, a study funder. "This gives you a clue about the nature of nicotine addictions."

While more study is needed to understand the gene's role in the metabolism of nicotine, he says the finding may lead to new medicines and treatments for people who are hooked.

The study also will lead to similar studies on other addictions such as alcohol.

"Individuals vary in their risk of addiction," says Edward Sellers, a study author. "There is evidence this gene defect causes this protection."

If scientists can find ways to mimic the faulty gene's work in those without the defect, they may be able to devise new drugs or treatments such as a pill that will keep people from breaking down the nicotine.

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