Smoking-associated bulky DNA adducts in bronchial tissue related to CYP1A1 MspI and GSTM1 genotypes in lung patients

Relationships between smoking status and levels of bulky DNA adducts wereinvestigated in bronchial tissue of lung patients in relation to theirGSTM1 and CYP1A1 MspI genotypes. A total of 150 Hungarian patientsundergoing pulmonary surgery were included in the study, 124 with lungmalignancies and 26 with non-malignant lung conditions. There weresignificant relationships between smoking status and bulky DNA adductlevels, as determined by 32P-post-labelling analysis, in macroscopicallynormal bronchial tissues. There was a highly significant difference in theadduct levels of a combined group consisting of current smokers andshort-term ex-smokers (< or = 1 year abstinence) compared with life-timenon-smokers and long-term ex- smokers (> 1 year abstinence) (P =0.0001). The apparent half-life was estimated to be 1.7 years for bulky DNAadducts in the bronchial tissue from ex-smokers. There were nostatistically significant correlations between (i) daily cigarette dose andDNA adduct levels in current smokers, (ii) DNA adduct level andhistological type of lung cancer, or (iii) GSTM1 and CYP1A1 MspI genotypesand DNA adduct levels after adjustment for either smoking status ormalignancy. By multiple logistic regression analysis, smoking and GSTM1null genotype were found to be risk factors for squamous cell carcinoma.However, bulky DNA adduct levels in bronchial tissue did not appear to be astatistically-significant risk factor for the major histological types oflung cancer.