Neurology: Unmasking Elusive Enzyme Reveals Known Villain Epidemiology: Cancer Risk May Be Higher for Young Smokers Health Policy: Use of Hormone Replacement Therapy Not Determined by Clinical Factors Sowing Better Seeds Angiogenesis Inhibitors May Slow Clogging of Arteries Nipping Anorexia in the Bud Vitamins May Protect Against Heart Disease Microbial Enzymes Choosier than Believed Conference on Academic Values Set Town Meeting on Gay and Lesbian Issues To Be Held at HMS Appointments to Full and Endowed Professorships In Memoriam: Robert A. Dorwart Nobelists Tapped To Speak at Soma Weiss Day Program Honors and Advances News Brief Students Teach Community Youngsters About Good Oral Health Why Not Harvard Medical? Front Page

EPIDEMIOLOGY 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 shows. David Christiani 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 UCSF.     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 adducts—complexes 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 Christiani. 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 carcinogens—perhaps due to developmental stage—so 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 damage—and by extension, lung cancer risk—can 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. —Tom Reynolds Back to Top