Cigarette smoking is the major cause of mortality and morbidity. There are more than 3000 compounds including 30 carcinogens in cigarette smoke. Genetic susceptibility to cigarette smokeinduced cancers may result from polymorphisms in carcinogen metabolism and DNA repair. Nicotine, the primary compound in tobacco, is mainly metabolized to cotinine by polymorphically expressed CYP2A6. GSTM1 and CYP2A6 were reported to be associated with risk of cigarette-related cancers. In addition, GSTM1 was associated with increased frequency of chromosomal aberration (CA). In this study, we aimed to evaluate whether cigarette smoking causes damage to DNA and increases CA frequency and to investigate the relation with CYP2A6 and GSTM1 genotypes in 24 healthy subjects in a Turkish population. We also investigated the consumption of cigarettes by measuring nicotine and cotinine with gas chromatography (GC) and its correlate with the CYP2A6 genotype. Our results showed that there was a significant increase in CA frequency in smoker subjects compared to non-smoker subjects. We found that the ratio of nicotine/cotinine excretion tended to rise in CYP2A6-mutant subjects compared to CYP2A6-wild subjects. CA frequencies were not significantly different in GSTM1-positive and GSTM1-null subjects (p>0.05). However, there was a significant association between GSTM1-null genotype and cigarette smoking (>15 cigarettes/day). Our results suggest an association between smoking and the CYP2A6 polymorphism and also indicate that genotypes play a pivotal role in smoking-related DNA damage.