06/24/98
Gene defect is why some people never become smokers
By Patricia Reaney
LONDON, June 24 (Reuters) - Scientists have discovered why
some people never get addicted to cigarettes and why all smokers
do not develop tobacco-related cancers.
For some people, a common genetic defect reduces their
ability to metabolise nicotine, the addictive ingredient in
cigarettes, making them less likely to become smokers. 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 said 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.
``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, said in a
telephone interview.
The CYP2A6 gene produces an enzyme that metabolises
nicotine. If scientists could block the function of the enzyme
with a drug they may be able to prevent and treat people
addicted to tobacco.
``We're interested therapeutically because we believe we can
imitate the genetic defect and use this as a (drug) therapy,''
said Tyndale.
People addicted to cigarettes must adjust their smoking to
maintain constant blood and brain nicotine levels.
A drug that could block the metabolism of nicotine could
prevent people from becoming addicted to tobacco or could help
smokers maintain their nicotine level for much longer so they
would need fewer cigarettes, making it easier for them to
eventually quit.
Tyndale envisions the development of a pill that smokers
could take in the morning that would block the enzyme function
for upwards of 24 hours.
The researchers are testing how smoking behaviour can be
changed in humans. The next step would involve a pharmaceutical
company to commercialise any treatment.
Tyndale said if all goes well a drug therapy could be just a
few years away.
Further down the road the gene could be a target for gene
therapy.
The medical implications of an effective treatment to
prevent smoking are enormous.
Approximately one-third of the world's population smokes,
despite the link with lung cancer and respiratory and heart
diseases. Studies have shown that up to 80 percent of smokers
acquire the habit by the time they are 15 or 16 years old.
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. People
who have one functioning and one faulty gene also have the
defect.
Tyndale and her colleagues, Edward Sellers and Michael
Pianezza, studied 184 people who had never smoked and 244 people
who were addicted. They said 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,'' said Tyndale.
^REUTERS@
--
Judith Richards, London, Ontario, Canada
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