Study Links Gene Pattern to Strong Smoking Addiction

Health: Finding supports view that an impaired ability to feel pleasure
plays a role in the addictive process.

Why do some people find they can kick the smoking habit with ease, while
others find it almost impossible? The answer might lie in an unusual
genetic pattern in their brains, Texas researchers report today in a
finding that may lead to new ways to help break the chains of nicotine
addiction.

The genetic combination identified by researchers at the M.D. Anderson
Cancer Center in Houston helps control the so-called reward/pleasure center
in the brain, the team reports in the Journal of the National Cancer
Institute.

A similar genetic pattern has previously been associated with an increased
susceptibility to alcoholism, drug abuse, compulsive overeating and
pathological gambling.

Taken together, all of these findings suggest that the emotional center of
the brain in people with this genetic predisposition has an impaired
ability to perceive pleasurable sensations, according to Dr. Ernest Noble
of UCLA, who wrote an editorial about the Texas research in the same issue.

Such people "do not experience the normal pleasures or rewards of life,"
Noble said in an interview. "To compensate, they use substances like
alcohol, drugs and nicotine to stimulate the brain . . . to increase
rewards or pleasure."

The fact that such myriad behaviors are linked to a single gene, he added,
may explain why there are so many smokers in bars and so many people who
drink and smoke in casinos.

"For a long time, we have thought that smoking and drinking and drug abuse
were all bad habits that were environmentally determined," Noble said. "But
while the environment you are raised in contributes somewhat, what you
inherit from your mother and father is more important. They are not moral
weaknesses, but medical disorders just like any other medical problem."

The particular gene involved in the new study is not the only gene that
controls susceptibility to nicotine addiction, or addiction of any sort,
noted Dr. George Uhl of the National Institute on Drug Abuse. And genetics
may account for only about half of the susceptibility to nicotine
addiction, with the environment contributing the rest.

But the gene does provide a way to target individuals who require special
interventions to control or prevent smoking, he added.

Tobacco use is by far the largest preventable cause of death in the United
States, claiming more than 400,000 victims each year. "If we got a handle
on even a small fraction of that, even 10% to 15%, it would have a big
public health impact," Uhl said.

The key to the new findings is the gene for a protein called DRD2, one of
five known dopamine receptors. Dopamine is one of the major
neurotransmitters responsible for carrying signals from one cell in the
brain to another. It binds to receptors on the surface of brain cells,
triggering further activity.

Dr. Margaret Spitz and her colleagues at Anderson studied 157 newly
diagnosed lung cancer patients and compared them to 126 healthy individuals
matched for age, sex, race and smoking status. They found no major
differences in the DRD2 gene between the cancer patients and the healthy
controls.

But overall, they found that people who smoked were much more likely to
carry one variant of the DRD2 gene. Furthermore, those who carried a
related variant began smoking at an earlier age and were much less likely
to have attempted to quit.

"Even after years of smoking, some individuals are able to quit the habit
while others are unsuccessful despite their cessation efforts," Spitz said.
"This finding may explain why that occurs."

Dr. David Comings of the City of Hope Medical Center in Duarte reported
similar results two years ago, but the paper, in an obscure journal, has
been largely ignored. "I am very pleased that she has found the same
thing," he said Tuesday.

Interestingly, the same variants of the DRD2 gene have previously been
linked to other forms of addiction as well, ranging from drug abuse to
overeating. This suggests that individuals who exhibit these behaviors have
a common chemical abnormality in the brain that manifests itself in
different ways, Noble said.

The new results offer the possibility of screening people entering smoking
cessation programs, Spitz said. Those with the more common variants would
receive conventional efforts, while those with the addiction-linked
variants--who would thus find it harder to break the habit--would be
targeted for special efforts.

Noble has found, for example, that alcoholics with the smoking-related
variant can be successfully treated with bromocriptine, a drug that
stimulates the release of dopamine in the brain. "Their craving disappears,
their anxiety disappears and they become more amenable to treatment," he
said. The drug might have similar benefits in heavy smokers, he added.

Buproprion, a drug that has already received some use in smoking cessation
treatments, also stimulates dopamine release. But other drugs might be more
effective, he said. Drugs used for treating Parkinson's disease stimulate
dopamine release and might be candidates for an anti-smoking drug.

Despite the linkage of so many different behaviors to DRD2, Uhl cautioned
that "there are a lot of people who have grave doubts" about those
linkages. Researchers have also identified other genes that may be involved
with vulnerability to addiction to alcohol and drugs, and those discoveries
have muddied the waters.

And perhaps most important, some researchers who have looked for the same
kinds of genetic links reported by Noble, Comings and others have not been
able to find them. "But that is exactly what you would expect" if more than
one gene is involved, Comings pointed out. One researcher's population
might have a higher incidence of the DRD2 receptor variants, while a
different gene may be more important in another group.

Copyright Los Angeles Times