title: GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms in lung cancer patients from an environmentally polluted region of Poland: correlation with lung DNA adduct levels.
abstract: 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.
authors.affiliation: Department of Tumor Biology, Centre of Oncology - Institute, Gliwice, Poland. dorotab@rocketmail.com
authors.forename: D
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: K J
authors.initials: KJ
authors.lastname: Cole
authors.forename: D H
authors.initials: DH
authors.lastname: Phillips
authors.forename: C C
authors.initials: CC
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Chorazy
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts / Q000235:genetics* / Q000378:metabolism; D004198:Disease Susceptibility; D004785:Environmental Pollutants / Q000009:adverse effects / Q000378:metabolism*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011044:Poland; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D004785:Environmental Pollutants; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase