The CYP and GST genetic polymorphisms, controlling metabolism of
xenobiotics, are considered to influence an individual's susceptibility to environmental and occupational
carcinogens and predisposition to
cancer. In the study, the effect of the GSTM1, GSTP1,
CYP1A1 and
CYP2D6 polymorphisms was investigated in relation to
PAH-DNA adduct levels in non-tumourous lung tissue from
non-small cell lung cancer (NSCLC) patients living in the industrialized region of Upper Silesia, Poland. The level of adducts among smokers was significantly elevated when compared to non-smokers (P = 0.0005). Adduct levels correlated inversely with age of patients (P = 0.00001). The GSTP1 and
CYP2D6 polymorphisms had no influence on
DNA adduct levels. There was a significant relationship between high adduct levels and the combined GSTM1 (null)/
CYP1A1-
Ile/Val genotype in the
squamous cell carcinoma group (P = 0.028). An elevated number of adducts was found in patients with the GSTM1 (null)/CYP1Al-
Ile/Val genotype compared to the GSTM1 (null)/
CYP1A1-Ile/Ile carriers (P = 0.043). A higher frequency of the
CYP1A1-
Ile/Val and GSTM1 (null)/
CYP1A1-
Ile/Val genotypes was observed in patients with high adduct levels (P = 0.05 and P = 0.009, respectively). A significant prevalence of the GSTM1(null)/
CYP1A1-
Ile/Val carriers in the
adenocarcinoma group was found (P = 0.003). Thus, our findings imply that the GSTMI and
CYP1A1 exon 7 polymorphisms may influence
PAH-DNA adduct levels in target tissue from NSCLC patients, especially in the
squamous cell carcinoma group. Moreover, individuals carrying the GSTM1(null)/
CYP1A1-
Ile/Val genotype might exhibit a greater predisposition to a peripheral type of
lung cancer.