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, CYP1A 1 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. (...)
Mots-clés Pascal : Carcinome non petite cellule, Bronchopulmonaire, Pollution air, Gène TP53, Gène suppresseur tumeur, Mutation, Glutathione transferase, Transferases, Enzyme, Hydroxylase, Oxidoreductases, Expression génique, Variabilité génétique, Polymorphisme, Epidémiologie moléculaire, Pologne, Europe, Pathogénie, Non fumeur, Homme, Génotype, Appareil respiratoire pathologie, Poumon pathologie, Bronche pathologie, Tumeur maligne, Génétique, Gène CYP1A1, Gène CYP2D6, Gène WAF1, Gène CIP1
Mots-clés Pascal anglais : Non small cell carcinoma, Bronchopulmonary, Air pollution, TP53 Gene, Tumor suppressor gene, Mutation, Glutathione transferase, Transferases, Enzyme, Hydroxylase, Oxidoreductases, Gene expression, Genetic variability, Polymorphism, Molecular epidemiology, Poland, Europe, Pathogenesis, Non smoker, Human, Genotype, Respiratory disease, Lung disease, Bronchus disease, Malignant tumor, Genetics
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0387973
Code Inist : 002B11A. Création : 22/03/2000.