Adolescent smokers appear to be more susceptible tolong-term DNA damage associated with lung cancer than peoplewho start smoking as adults, according to a study led by aUC San Francisco researcher that examined DNA damage informer smokers who have lung cancer.
The study, published in the April 6 issue of Journal of theNational Cancer Institute, indicates that ex-smokers withlung cancer who began smoking in adolescence had higherlevels of chemically altered DNA in their lungs and bloodthan ex-smokers who started smoking later in life. Thestudy accounted for numerous variables, including the numberof years ex-smokers smoked and the amount they smoked.
"Our finding suggests that young smokers incur more severeor persistent DNA damage than adult smokers do", said thelead author of the study, John K. Wiencke, PhD, associateprofessor of epidemiology at UCSF.
"Smoking during adolescence may produce physiologic changesthat lead to persistent increased DNA damage, or youngsmokers may be markedly susceptible to DNA damage formationand have higher burdens of damage after they quit smokingthan those who started smoking later in life," said Wiencke.
All smokers develop some level of DNA damage, which is aknown risk factor for lung cancer, and all people who quitexperience some level of DNA repair. The current findingsuggests that less repair - or less successful repair -occurs in people who smoked as adolescents.
The finding was drawn from a broader investigation thatsought to parse out correlations between the variouspossible factors contributing to lung cancer - such as yearsand intensity of smoking--and DNA damage in the lungs.
"The ability to identify those current and former smokerswith the highest risk of developing cancer has substantialpreventive implications," said Wiencke.
The damaged, or chemically altered segments of DNA, known asDNA adducts, are physical complexes in genes that are knownto result from exposure to carcinogens, and they arebelieved to be one of the first steps in the carcinogenicpathway that ultimately leads to tumor formation. In tobaccosmoke, carcinogens known as polynuclear aromatichydrocarbons (PAHs) bind to such genes as p53 and arestrongly suspected of initiating lung tumor formation.
The researchers conducted their study by examining DNAadduct levels in nontumorous lung tissue samples from 143lung cancer patients and blood samples from fifty-seventhese patients. Fifty-seven of the patients were currentsmokers, 79 were ex-smokers and seven had never smoked.
In the lung tissue of people who had never smoked, DNAadduct levels were low; in current smokers, they were eighttimes higher; and, in ex-smokers, they were 3.5 timeshigher.
In current smokers, a high number of cigarettes smoked perday was the variable most closely related to high adductlevels.
In former smokers, however, the age at which a person begansmoking was the strongest indicator of DNA adduct levels. Highest levels of DNA damage were observed in individualswho began smoking between the ages of 9 and 12 years.
The researchers propose two possible explanations for whyage might impact smoking-related DNA adduct levels. Onepossibility is that smoking at an early age, a time of rapidlung growth and development, induces long-lastingphysiologic changes that impair the removal of damaged unitsin the DNA. Another possibility is that very young smokersaccumulate more damaged DNA, and that, even with repair, thedamage remains many years after smoking cessation, incontrast to subjects who begin to smoke later. Neither ofthese mechanism has been examined in humans.
The authors also determined that levels of DNA adducts incirculating blood cells have a higher statisticalcorrelation with levels in the lung tissue samples,indicating that measurements from blood cells may well actas a reliable indicator of DNA adduct levels in tissue.
Overall, the findings should fuel efforts to pinpoint howprecisely DNA adduct levels correlate with the variousfactors suspected of contributing to individualsusceptibility to lung cancer, including smoking history,genetics, diet and occupation and now, perhaps age at whichsmoking occurs.
"To our knowledge, no other study has considered the age atwhich smoking was initiated as a potential predictor oftobacco smoke-related DNA damage in former smokers," saidWiencke.
Co-authors of the study were Andrea Varkonyi, of theLaboratory for Molecular Epidemiology, Department ofEpidemiology and Biostatistics, at UCSF; Sally W. Thurstonand Karl T. Kelsey, Harvard School of Public Health; John C.Wain, Massachusetts General Hospital; Eugene J. Mark,Harvard Medical School; and David C. Christiani, HarvardSchool of Public Health, Massachusetts General Hospital andHarvard Medical School.
The study was funded by the National Institute ofEnvironmental Health Sciences, the National CancerInstitute, the National Institutes of Health, and theDepartment of Health and Human Services.
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