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 χ 2 ). 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. © 1999 Cancer Research Campaign

Increased risk of non-small cell lung cancer and frequency of somatic TP53 gene mutations in Pro72 carriers of TP53 Arg72Pro polymorphism

“…The percentage of TP53 gene mutations found in this study (32%) was lower than in another Polish study including patients from the Silesian region [20], known for its heavy environmental pollution, but within the range of other studies in NSCLC [7,[21][22][23].…”

Clinical Significance of the p53 Pathway and Associated Gene Therapy in Non-Small Cell Lung Cancers

“…In fact, previous clinical studies in NSCLCs have demonstrated p21 expression to be an indicator for the effectiveness of chemotherapy [89] and future science group future science group www.futuremedicine.com adenoviral p53 gene therapy [41]. However, several clinical studies in NSCLCs have found no correlation between p21 expression and p53 mutations or p53 protein overexpression [90,91]. These results might be due to simple evaluations of the p53 status only.…”

Impact of AhR, CYP1A1 and GSTM1 Genetic Polymorphisms on TP53 R273G Mutations in Individuals Exposed to Polycyclic Aromatic Hydrocarbons

“…It was also shown that the p53 gene is more frequently mutated in lung cancer patients with the CYP1A1 Val/Val genotype according to the reports described by Kawajirii et al (1996) and Przygodzki et al (1998). However, Rusin and his colleagues have not detected the similar relationship in non-small-cell lung cancer from an environmentally polluted region of Poland (Rusin et al, 1999). Although the GSTM1null genotype has been correlated with increased risk for p53mutations, this association has not been observed in all studies.…”