GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms in lung cancer patients froman environmentally polluted region of Poland: correlation with lung DNA adduct levels

The CYP and GST genetic polymorphisms, controlling metabolism of xenobiotic s, are considered to influence an individual's susceptibility to environmen tal and occupational carcinogens and predisposition to cancer. In the study , the effect of the GSTM1, GSTP1, CYB1A1 and CYP2D6 polymorphisms was inves tigated in relation to PAH-DNA adduct levels in non-tumourous lung tissue f rom non-small cell lung cancer (NSCLC) patients living in the industrialize d region of Upper Silesia, Poland. The level of adducts among smokers was s ignificantly elevated when compared to non-smokers (P = 0.0005). Adduct lev els correlated inversely with age of patients (P = 0.00001). The GSTP1 and CYP2D6 polymorphisms had no influence on DNA adduct levels. There was a sig nificant relationship between high adduct levels and the combined GSTM1 (nu ll)/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 )/CYP1A1-Ile/Val genotype compared to the GSTM1 (null)/CYP1A1-Ile/Ile carri ers (P = 0.043). A higher frequency of the CYP1A1-Ile/Val and GSTM1 (null)/ CYP1A1-Ile/Val genotypes was observed in patients dth 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 GSTM1 and CYP1A1 exon 7 polymorph isms may influence PAH-DNA adduct levels in target tissue from NSCLC patien ts, especially in the squamous cell carcinoma group. Moreover, individuals carrying the GSTM1 (null)/CYP1A1-Ile/Val genotype might exhibit a greater p redisposition to a peripheral type of lung cancer. (C) 1999 Lippincott Will iams & Wilkins.