DNA adduct level in lung tissue may act as a risk biomarker of lung cancer

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 bioma rker for the development of lung cancer. To verify this hypothesis, the aro matic/hydrophobic DNA adduct levels of non-tumorous adjacent lung tissues f rom 73 primary lung cancer patients and 33 non-cancer controls were evaluat ed by P-32-postlabelling assay. Wilcoxon rank sum test showed that DNA addu ct 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 ca ncer and non-cancer samples were not influenced by smoking behaviour and ci garette consumption. Our data. also showed that the polymorphisms of cytoch rome P4501A1 (CYP1A1) Msp1, glutathione S-transferase M1 (GSTM1) and the co mbination of both genetic polymorphisms were not related to the DNA adduct levels. Interestingly, positive association between CYP1A1 protein expressi on and DNA adduct levels was found when CYP1A1 protein expression in lung s pecimens from lung cancer patients was examined by immunohistochemistry. Mu ltivariate linear regression analysis indicated that the DNA adduct level w as not associated with gender, smoking behaviour, or genetic polymorphisms of CYP1A1 and GSTM1. Moreover, multivariate logistic regression analysis sh owed that persons with high DNA adduct levels (> 48.66 adducts/10(8) nucleo tides) had an approximately 25-fold risk of lung cancer compared with perso ns with low DNA adduct levels (less than or equal to 48.66 adducts/10(8) nu cleotides). In conclusion, DNA adduct levels in lung tissue may be a more r eliable lung cancer susceptibility biomarker than DNA adduct levels in leuc ocytes. In addition, higher susceptibility to DNA damage in lung cancer pat ients may partly play a role in the development of lung cancer. (C) 2000 El sevier Science Ltd. All rights reserved.