Adolescent smokers appear to be more susceptible to long-term DNA damage associated with lung cancer than people who start smoking as adults, according to a study led by a UC San Francisco researcher that examined DNA damage in former smokers who have lung cancer.
The study, published in the April 6 issue of Journal of the National Cancer Institute, indicates that ex-smokers with lung cancer who began smoking in adolescence had higher levels of chemically altered DNA in their lungs and blood than ex-smokers who started smoking later in life. The study accounted for numerous variables, including the number of years ex-smokers smoked and the amount they smoked.
"Our finding suggests that young smokers incur more severe or persistent DNA damage than adult smokers do," said the lead author of the study," John K. Wiencke, PhD, associate professor of epidemiology at UCSF.
"Smoking during adolescence may produce physiologic changes that lead to persistent increased DNA damage, or young smokers may be markedly susceptible to DNA damage formation and have higher burdens of damage after they quit smoking than those who started smoking later in life," said Wiencke.
All smokers develop some level of DNA damage, which is a known risk factor for lung cancer, and all people who quit experience some level of DNA repair. The current finding suggests that less repair - or less successful repair - occurs in people who smoked as adolescents.
The finding was drawn from a broader investigation that sought to parse out correlations between the various possible factors contributing to lung cancer - such as years and intensity of smoking--and DNA damage in the lungs.
"The ability to identify those current and former smokers with the highest risk of developing cancer has substantial preventive implications," said Wiencke. The damaged, or chemically altered segments of DNA, known as DNA adducts, are physical complexes in genes that are known to result from exposure to carcinogens, and they are believed to be one of the first steps in the carcinogenic pathway that ultimately leads to tumor formation. In tobacco smoke, carcinogens known as polynuclear aromatic hydrocarbons (PAHs) bind to such genes as p53 and are strongly suspected of initiating lung tumor formation.
The researchers conducted their study by examining DNA adduct levels in nontumorous lung tissue samples from 143 lung cancer patients and blood samples from fifty-seven these patients. Fifty-seven of the patients were current smokers, 79 were ex-smokers and seven had never smoked.
In the lung tissue of people who had never smoked, DNA adduct levels were low; in current smokers, they were eight times higher; and, in ex-smokers, they were 3.5 times higher.
In current smokers, a high number of cigarettes smoked per day was the variable most closely related to high addict levels.
In former smokers, however, the age at which a person began smoking was the strongest indicator of DNA adduct levels. Highest levels of DNA damage were observed in individuals who began smoking between the ages of 9 and 12 years.
The researchers propose two possible explanations for why age might impact smoking-related DNA adduct levels. One possibility is that smoking at an early age, a time of rapid lung growth and development, induces long-lasting physiologic changes that impair the removal of damaged units in the DNA.
Another possibility is that very young smokers accumulate more damaged DNA, and that, even with repair, the damage remains many years after smoking cessation, in contrast to subjects who begin to smoke later. Neither of these mechanism has been examined in humans.
The authors also determined that levels of DNA adducts in circulating blood cells have a higher statistical correlation with levels in the lung tissue samples, indicating that measurements from blood cells may well act as a reliable indicator of DNA adduct levels in tissue.
Overall, the findings should fuel efforts to pinpoint how precisely DNA adduct levels correlate with the various factors suspected of contributing to individual susceptibility to lung cancer, including smoking history, genetics, diet and occupation and now, perhaps age at which smoking occurs.
"To our knowledge, no other study has considered the age at which smoking was initiated as a potential predictor of tobacco smoke-related DNA damage in former smokers," said Wiencke.
Co-authors of the study were Andrea Varkonyi, of the Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, at UCSF; Sally W. Thurston and Karl T. Kelsey, Harvard School of Public Health; John C. Wain, Massachusetts General Hospital; Eugene J. Mark, Harvard Medical School; and David C. Christiani, Harvard School of Public Health, Massachusetts General Hospital and Harvard Medical School.
The study was funded by the National Institute of Environmental Health Sciences, the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services.
Journal
JNCI Journal of the National Cancer Institute