title: Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland.
abstract: The p53 mutation spectrum can generate hypotheses linking carcinogen exposure to human cancer. Although it is well-documented that tobacco smoking is a major cause of lung cancer, the contribution of air pollution is less well-established. We determined the molecular and immunohistochemical changes (p53 gene mutations, p53 protein accumulation and WAF1 protein expression) and genetic polymorphisms of GSTM1, CYP1A1 and CYP2D6 genes in a case series of non-small-cell lung cancers from Silesia. This region of southern Poland is highly industrialized with considerable environmental pollution. More than 50% of lung cancers (90/164) contained p53 mutations and 75% showed the combined alteration of the p53 gene and protein accumulation. Males occupationally exposed to coal-derived substances showed a relatively high frequency of squamous and large-cell carcinomas, relatively frequent mutations in codon 298 of p53 and a low frequency of p53 immunohistochemically positive tumours. Codon 298 GAG-->TAG mutations have rarely been found in lung cancers in other populations. We found no correlation between WAF1 protein expression and mutations in the p53 gene or p53 protein accumulation. No statistically significant relationship was found between p53 mutations and GSTM1, CYP1A1, CYP2D6 genotypes. Never smokers with lung cancers from Silesia had a higher frequency of G:C-->T:A transversions than previously reported of the p53 mutation spectrum in never smokers (6/15 vs 4/34; P = 0.06 by chi2). These data are a tentative indication that occupational and environmental exposure to polycyclic aromatic hydrocarbons, such as benzo(a)pyrene, in polluted air contributes to the molecular pathogenesis of lung cancer in never smokers.
authors.affiliation: Department of Tumour Biology, Institute of Oncology, Gliwice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Rusin
authors.forename: D
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: E
authors.initials: E
authors.lastname: Malusecka
authors.forename: A
authors.initials: A
authors.lastname: Zborek
authors.forename: J
authors.initials: J
authors.lastname: Harasim
authors.forename: K
authors.initials: K
authors.lastname: Czyzewski
authors.forename: W P
authors.initials: WP
authors.lastname: Bennett
authors.forename: P G
authors.initials: PG
authors.lastname: Shields
authors.forename: A
authors.initials: A
authors.lastname: Weston
authors.forename: J A
authors.initials: JA
authors.lastname: Welsh
authors.forename: S
authors.initials: S
authors.lastname: Krzyzowska-Gruca
authors.forename: M
authors.initials: M
authors.lastname: Chorazy
authors.forename: C C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology*; D003031:Coal; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D016158:Genes, p53; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D009154:Mutation; D016273:Occupational Exposure; D012907:Smoking / Q000009:adverse effects
chemical_list: C493956:CDKN1A protein, human; D003031:Coal; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase