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Cancer Risk May Be Higher
For Young Smokers
Cigarette smokers who take up the habit
in adolescence may face a greater risk of lung cancer than late
starters, even long after quitting, a new study by Harvard researchers
and coworkers found that measurements of DNA damage from
smoking in blood cells correlates closely with levels
measured in lung tissue. This means researchers will be
better able to study the damage from smoking in people
who have not developed lung cancer.
The findings provide yet another reason for young
people to avoid tobacco, says David Christiani, professor of occupational
medicine and epidemiology at the Harvard School of Public Health.
They might also lend weight to the argument that state funds from
tobacco industry settlements should be spent largely on smoking
prevention among young people. Christiani heads a multidisciplinary
program exploring genetic susceptibility to lung cancer, of which
the new study is part. The lead author of the article, published
in the April 7 Journal of the National Cancer Institute,
is John K. Weincke of the University of California, San Francisco.
Co-authors are at HSPH, HMS, Massachusetts General Hospital, and
The researchers examined DNA damage in lung and
blood cells of lung cancer patients who were either current smokers,
ex-smokers, or nonsmokers. Specifically, they measured aromatic
hydrophobic DNA adductscomplexes of tobacco carcinogens with DNA
that are believed to represent an early step in carcinogenesis.
The study aimed at defining the influence on DNA adduct measurements
of variables such as duration of smoking, number of cigarettes smoked
per day, and age at smoking initiation, and was the first to look
at the effects of initiation age. Adducts accumulate in active smokers
but begin to diminish once a smoker quits, as a result of DNA repair
and cell turnover. Another aim was to compare lung and blood cell
measurements, to determine whether blood levels can serve as a good
surrogate for levels in the target tissue, the lungs.
As expected, smokers in the study had the highest
adduct levels, "never-smokers" had the lowest, and former
smokers, who had quit about 12 years before on average, had intermediate
levels. For current smokers, smoking intensity was the best predictor
of adduct levels. But for ex-smokers, whose adduct levels were slightly
less than half those of current smokers, age at initiation was most
important, even after controlling for years since quitting. (This
age effect may be at work in current smokers, too, but it could
not be observed in the analysis because smoking intensity is a more
powerful effect in this group, Christiani explains.)
The findings provide
yet another reason for young people to avoid tobacco, says David
Vulnerability of Youth
The researchers propose two possible explanations for the finding.
The lungs of young smokers may be especially susceptible to damage
from tobacco carcinogensperhaps due to developmental stageso
that they accumulate more DNA adducts. The other possibility is
that adducts are more persistent in younger lungs, which might be
a result of less efficient repair of DNA damage. Although laboratory
studies have not been done to evaluate these hypotheses, epidemiologic
evidence supports the idea that early smoking initiation increases
risk of lung cancer, Christiani notes. The problem is that it is
difficult to disentangle the effects of age at initiation from those
of total tobacco exposure.
Another important finding
was that aromatic hydrophobic DNA adduct levels measured in blood
mononuclear cells correlate closely with levels measured in lung
tissue from the same individual. This means that DNA damageand
by extension, lung cancer riskcan be assessed without taking tissue
directly from the lung, allowing studies to be done on people who
have not developed lung cancer.
"Novel molecular approaches to evaluate
tobacco smoke exposure in children and adolescents could be extremely
useful in understanding cancer susceptibility associated with carcinogen
exposures early in life," the authors write.
Another implication of the study is that researchers
should consider current and former smokers separately in data analyses
of DNA adduct measurements, the authors note, because the variables
affecting their adduct levels are different.
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