Can't quit smoking? Blame your genes
New studies show ‘double whammy' link to addiction andcancerWASHINGTON-
Scientists say they havepinpointed a genetic link that makes peoplemore likely
to get hooked ontobacco, causing them to smoke morecigarettes, making it harder
to quit,and leading more often to deadlylung cancer.
The discovery by three separate teams of scientistsmakes the strongestcase so
far for the biological underpinnings of theaddiction of smokingand sheds light
on how genetics and cigarettes joinforces to causecancer, experts said. The
findings also lay thegroundwork for moretailored quit-smoking treatments.
"This iskind of a double whammy gene,'' said Christopher Amos, aprofessor
ofepidemiology at the M.D. Anderson Cancer Center in Houstonand author ofone of
the studies. "It also makes you more likely tobe dependent onsmoking and less
likely to quit smoking.''
Greater cancer risk
Asmoker who inherits this genetic variation from both parents has an80percent
greater chance of lung cancer than a smoker withoutthevariants, the researchers
reported. And that same smoker onaveragelights up two extra cigarettes a day
and has a much harder timequittingthan smokers who don't have these genetic
differences.
Thethree studies, funded by governments in the U.S. and Europe,
arebeingpublished Thursday in the journals Nature andNatureGenetics.
Thescientists surveyed genetic markers in more than 35,000 peopleinEurope,
Canada and the United States, zeroing in on the same setofgenetic differences.
They aren't quite sure if what they found is asetof variations in one gene or
in three closely connected genes. Buttheysaid the result is the same: These
genetic quirks increase the riskofaddiction and lung cancer.
The studies' authors disagreedon whether the set of variants directlyincreased
the risk of lungcancer or did so indirectly by causing moresmoking that led to
thecancer.
The genetic variations, which encode nicotine receptorson cells,
couldeventually help explain some of the mysteries of chainsmoking,
nicotineaddiction and lung cancer that can't be chalked up
toenvironmentalfactors, brain biology and statistics, experts said.
Theseodditiesinclude why there are 100-year-old smokers who don't get
cancerandpeople who light up an occasional cigarette and don't gethooked.
In the last 40 years, the rate of adult Americans smoking has been cutfrom 42
percent in 1965 to less than 21 percent now.
Thenew studies point to surprising areas of the genes not
associatedwithpleasure and addiction rewards. That may help explain why
peoplehavetrouble quitting, said Dr. Nora Volkow, director of
theNationalInstitute of Drug Abuse in Bethesda, Md., which funded one
ofthestudies. Eventual testing for the genetic variants could lead
tocustomtreatments for quitting smoking.
"This is really tellingus that the vulnerability to smoking and howmuch you
smoke is clearlybiologically based,'' said psychiatry professorDr. Laura
Bierut, ofWashington University in St. Louis, and a geneticsand smoking
expertwho did not take part in the studies. She praised theresearch as
"veryintriguing.''
The studies mostly looked at smokers andex-smokers although two of thestudies
also looked at several hundrednonsmokers. The research onlyinvolved white
people of European descent.People of Asian and Africandescent will be studied
soon and may yieldquite different results,scientists said. Smoking-related
diseasesworldwide kill about one in 10adults, according to the World
HealthOrganization.
The studies show on average the consequences ofthe set of variations inthe
alphabet of genetic code that peopleinherit from each parent:Smokers
who get the set of variants from only one parent see a riskof lung
cancer that is about one-third higher than people without anyvariants.
They also smoke about one more cigarette a day on average thanother
smokers. This group makes up about 45 percent of the populationstudied.Smokers
who inherit the variants from both parents have almost a onein four
chance of developing lung cancer.. Their risk is between 70 and
80percent higher than the cancer risk of other smokers without the
geneticvariants. They smoke on average of two extra cigarettes a day,
and have a45 percent higher risk of peripheral artery disease. This
group accountsfor about one in nine people of European descent.Smokers
who don't have the variants are still more than 10 times morelikely to
get lung cancer than nonsmokers. Smokers without the variantoverall
have about a 14 percent risk of getting lung cancer. Bycomparison, the
risk of lung cancer for people who have never smoked isless than 1
percent, said another study author, Paul Brennan of theInternational
Agency for Research onCancer in Lyon, France.
Brennanand Amos, working on different teams, linked the geneticvariationitself
when triggered by smoking directly to lung cancer.Brennansaid the nicotine
receptors that the variants acton also canstimulatetumor growth.
Brennan'sstudy also found that lung cancer risk for nonsmokers with
thevariantswas higher than for those without the variants. However,
hissmallsample size of nonsmokers requires further study. Amos' studydidn'tfind
increased lung cancer risk for people with the set ofvariants whohave never
smoked.
ButKari Stefansson, lead author of the largest of the three studiesandchief
executive of deCode Genetics of Iceland, said the increasedlungcancer risk was
indirect, and that the variant caused moreaddiction andmore smoking. It was the
extra cigarettes from increaseddaily smokingand the inability to quit that
contributed to the highercancer risk,Stefansson said.
"It's very likely that in the endthere's going to be a test andthis is going to
be folded into a panelof tests for the risk ofcancers,'' said Stefansson, whose
companyalready does prostate cancergenetic tests. The tests will lead tobetter
treatments, but probably notprevention of smoking, he said.
Stefanssonand others emphasize that people without the variants shouldnot
takethat genetic finding as a green light to smoke.There
areothersmoking-related diseases and they would still be a thigh risk
oflungcancer.
For Stefansson, the research hits home. His father,a smoker,died of lungcancer.
And Stefansson, who doesn't smoke,frequently lectures his23-year-old daughter
"who smokes like achimney.'' She acts like sheis immortal and smoking can't
kill her,Stefansson said. But his ownresearch shows that her genes are
probablystacked against her.
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