p53 mutation spectrum in relation to GSTM1, CYP1A1 and CYP2E1 in surgically treated patients with non-small cell lung cancer

p53 mutation status was analysed in relation to DNA polymorphisms of GSTM1, CYP1A1 and CYP2E1 from 105 surgically resected non-small cell lung cancer cases. Demographic factors, smoking, occupation, family history, tumour his tology, grade and stage were taken into account. p53 mutations, detected ei ther directly by DNA sequencing (P = 0.04, adjusted for smoking) or indirec tly by immunostaining (P = 0.06), were overrepresented among CYP1A1 variant s. Mutations in exon 8 and transitions at CpG sites in the p53 gene were fa voured in this subset. There was no relation between the individual gene po lymorphisms or p53 mutations and disease-free survival by Kaplan-Meier anal ysis, The finding of excess CYP1A1 heterozygotes in individuals with p53 mu tations after adjustment for smoking suggests that CYP1A1 activation contri butes to lung cancer via p53 inactivation. Pharmacogenetics 8:503-511. (C) 1998 Lippincott Williams & Wilkins.