Early age at smoking initiation and tobacco carcinogen DNA damage in the lung

Background: DNA adducts formed as a consequence of exposure to tobacco smok e may be involved in carcinogenesis, and their presence may indicate a high risk of lung cancer, To determine whether DNA adducts can be used as a "do simeter" for cancer risk, we measured the adduct levels in nontumorous lung tissue and blood mononuclear cells from patients with lung cancer, and we collected data from the patients on their history of smoking. Methods: We u sed the P-32-postlabeling assay to measure aromatic hydrophobic DNA adducts in nontumorous lung tissue from 143 patients and in blood mononuclear cell s from 54 of these patients, From the smoking histories, we identified expo sure variables associated with increased DNA adduct levels by use of multiv ariate analyses with negative binomial regression models, Results/ Conclusi ons: We found statistically significant interactions for variables of curre nt and former smoking and for other smoking variables (e.g., pack-years [nu mber of packs smoked per day x years of smoking] or years smoked), indicati ng that the impact of smoking variables on DNA adduct levels may be differe nt in current and former smokers. Consequently, our analyses indicate that models for current and former smokers should be considered separately. In c urrent smokers, recent smoking intensity (cigarettes smoked per day) was th e most important variable. In former smokers, age at smoking initiation was inversely associated with DNA adduct levels. A highly statistically signif icant correlation (r =.77 [Spearman's correlation]; two sided P<.001) was o bserved between DNA adduct levels in blood mononuclear cells and lung tissu e. Implications: Our results in former smokers suggest that smoking during adolescence may produce physiologic changes that lead to increased DNA addu ct persistence or that young smokers may be markedly susceptible to DNA add uct formation and have higher adduct burdens after they quit smoking than t hose who started smoking later in life.