Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland

The p53 mutation spectrum can generate hypotheses linking carcinogen exposu re 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 wel l-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 serie s of non-small-cell lung cancers from Silesia. This region of southern Pola nd is highly industrialized with considerable environmental pollution. More than 50% of lung cancers (90/164) contained p53 mutations and 75% showed t he combined alteration of the p53 gene and protein accumulation. Males occu pationally exposed to coal-derived substances showed a relatively high freq uency of squamous and large-cell carcinomas, relatively frequent mutations in codon 298 of p53 and a low frequency of p53 immunohistochemically positi ve tumours. Codon 298 GAG--> TAG mutations have rarely been found in lung c ancers in other populations. We found no correlation between WAF1 protein e xpression and mutations in the p53 gene or p53 protein accumulation. No sta tistically significant relationship was found between p53 mutations and GST M1, 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 c hi(2)). These data are a tentative indication that occupational and environ mental exposure to polycyclic aromatic hydrocarbons, such as benzo(a)pyrene , in polluted air contributes to the molecular pathogenesis of lung cancer in never smokers.