Genetic Link Tied to Smoking Addiction
By SETH BORENSTEIN - 6 hours ago
WA****NGTON (AP) - Scientists have pinpointed genetic variations that make
people more likely to get hooked on cigarettes and more prone to develop
lung cancer - a finding that could someday lead to screening tests and
customized treatments for smokers trying to kick the habit.
The discovery by three separate teams of scientists makes the strongest
case
so far for the biological underpinnings of nicotine addiction and sheds
more
light on how genetics and lifestyle habits join forces to cause cancer.
"This is kind of a double whammy gene," said Christopher Amos, a professor
of epidemiology at the M.D. Anderson Cancer Center in Houston and author
of
one of the studies. "It also makes you more likely to be dependent on
smoking and less likely to quit smoking."
A smoker who inherits these genetic variations from both parents has an 80
percent greater chance of lung cancer than a smoker without the variants,
the researchers re****ted. And that same smoker on average lights up two
extra cigarettes a day and has a much harder time quitting than smokers
who
don't have these genetic differences.
The researchers disagreed on whether the variants directly increased the
risk of lung cancer or did so indirectly, by causing more smoking.
The three studies, funded by governments in the U.S. and Europe, are being
published Thursday in the journals Nature and Nature Genetics.
The scientists studied the genes of more than 35,000 white people of
European descent in Europe, Canada and the United States. Blacks and
Asians
will be studied soon and may yield different results, scientists said.
They aren't quite sure if what they found is a set of variations in one
gene
or in three closely connected genes.
The gene variations, which govern nicotine receptors on cells, could
eventually help explain some of the mysteries of chain smoking, nicotine
addiction and lung cancer. These oddities include why there are
90-year-old
smokers who don't get cancer and people who light up an occasional
cigarette
and don't get hooked.
"This is really telling us that the vulnerability to smoking and how much
you smoke is clearly biologically based," said psychiatry professor Dr.
Laura Bierut of Wa****ngton University in St. Louis, a genetics and smoking
expert who did not take part in the studies. She praised the research as
"very intriguing."
The smoking rate among U.S. adults has dropped from 42 percent in 1965 to
less than 21 percent now.
The new studies are surprising in that they point to areas of the genetic
code that are not associated with pleasure and the rewards of addiction.
That may help explain why some people can quit and others fail, said Dr.
Nora Volkow, director of the National Institute of Drug Abuse in Bethesda,
Md., which funded one of the studies.
"It opens our eyes," Volkow said Wednesday. "Not everyone takes drugs for
the same reason. Not everyone smokes cigarettes for the same reasons."
One clue is in the location of the just-discovered variants, on the long
arm
of chromosome 15, Volkow said. It is in an area that, when damaged during
tests on animals, makes them depressed and anxious. While some people
smoke
because it helps them focus or gives them a physiological reward, others
do
it to stave off depression.
That suggests that adding antidepressants to some smokers' treatment could
help them kick the habit.
Bierut said a simple, inexpensive test could be developed to screen people
for the variants. Kari Stefansson, lead author of the largest of the three
studies, agreed. He is chief executive of deCode Genetics of Iceland,
which
already does prostate cancer genetic tests.
Such testing could carry risks all its own, bioethicist Arthur Caplan of
the
University of Pennsylvania warned. People who have been found to have a
genetic predisposition to addiction and lung cancer could find it harder
to
get health or life insurance, or their employer might drop their coverage,
he said.
"The good news is that getting these risk estimates will help focus
anti-smoking campaigns, and some people will want to voluntarily get into
anti-addiction programs early, where they will probably work better,"
Caplan
said in an e-mail. But if such testing is done, it should be voluntary,
and
the results should be kept private, he said.
Smoking-related diseases worldwide kill about one in 10 adults, according
to
the World Health Organization.
Among the findings:
_ Smokers who get the set of variants from only one parent see a risk of
lung cancer that is about one-third higher than that of people without the
variants. They also smoke about one more cigarette a day on average than
other smokers. This group makes up about 45 percent of the population
studied.
_ Smokers who inherit the variants from both parents have nearly a 1-in-4
chance of developing lung cancer. Their cancer risk is 70 to 80 percent
higher than that of smokers without the genetic variants. They smoke on
average two extra cigarettes a day. This group accounts for about one in
nine people of European descent.
_ Smokers who don't have the variants are still more than 10 times more
likely to get lung cancer than nonsmokers. Smokers without the variant
have
about a 14 percent risk of getting lung cancer. The risk of lung cancer
for
people who have never smoked is less than 1 percent, said another study
author, Paul Brennan of the International Agency for Research on Cancer in
Lyon, France.
Brennan and Amos, working on different teams, linked the genetic variation
itself - when triggered by smoking - directly to lung cancer. Brennan said
the nicotine receptors that the variants act on also can stimulate tumor
growth.
But Stefansson said the increased lung cancer risk was indirect - the
variants led to more smoking, which led to more cancer.
For Stefansson, the research hits home. His father, a smoker, died of lung
cancer. And Stefansson, who doesn't smoke, frequently lectures his
23-year-old daughter "who smokes like a chimney." She acts as if she is
immortal and smoking can't kill her, Stefansson said. But his own research
shows that her genes are probably stacked against her.
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