Lung cancer is a leading cause of mortality in Taiwan. We hypothesised that high susceptibility to DNA damage in the target organ acts as a risk biomarker for the development of lung cancer. To verify this hypothesis, the aromatic/hydrophobic DNA adduct levels of non-tumorous adjacent lung tissues from 73 primary lung cancer patients and 33 non-cancer controls were evaluated by 32P-postlabelling assay. Wilcoxon rank sum test showed that DNA adduct levels in lung cancer patients (49.58+/-33.39 adducts/10(8) nucleotides) were significantly higher than those in non-cancer controls (18.00+/-15.33 adducts/10(8) nucleotides, P<0.001). The DNA adduct levels among lung cancer and non-cancer samples were not influenced by smoking behaviour and cigarette consumption. Our data also showed that the polymorphisms of cytochrome P4501A1 (CYP1A1) Msp1, glutathione S-transferase M1 (GSTM1) and the combination of both genetic polymorphisms were not related to the DNA adduct levels. Interestingly, positive association between CYP1A1 protein expression and DNA adduct levels was found when CYP1A1 protein expression in lung specimens from lung cancer patients was examined by immunohistochemistry. Multivariate linear regression analysis indicated that the DNA adduct level was not associated with gender, smoking behaviour, or genetic polymorphisms of CYP1A1 and GSTM1. Moreover, multivariate logistic regression analysis showed that persons with high DNA adduct levels (>48.66 adducts/10(8) nucleotides) had an approximately 25-fold risk of lung cancer compared with persons with low DNA adduct levels (</=48.66 adducts/10(8) nucleotides). In conclusion, DNA adduct levels in lung tissue may be a more reliable lung cancer susceptibility biomarker than DNA adduct levels in leucocytes. In addition, higher susceptibility to DNA damage in lung cancer patients may partly play a role in the development of lung cancer.