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

Ronald M. Przygodzki, William P. Bennett, Donald G. Guinee, Mohammed A. Khan, Andrew Freedman, Peter G. Shields, William D. Travis, James R. Jett, Henry Tazelaar, Peter Pairolero, Victor Trastek, Lance A. Liotta, Curtis C. Harris, Neil E. Caporaso

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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 histology, grade and stage were taken into account. p53 mutations, detected either directly by DNA sequencing (P = 0.04, adjusted for smoking) or indirectly by immunostaining (P = 0.06), were overrepresented among CYP1A1 variants. Mutations in exon 8 and transitions at CpG sites in the p53 gene were favoured in this subset. There was no relation between the individual gene polymorphisms or p53 mutations and disease-free survival by Kaplan-Meier analysis. The finding of excess CYP1A1 heterozygotes in individuals with p53 mutations after adjustment for smoking suggests that CYP1A1 activation contributes to lung cancer via p53 inactivation.

Original languageEnglish (US)
Pages (from-to)503-511
Number of pages9
JournalPharmacogenetics
Volume8
Issue number6
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • CYP1A1
  • CYP2E1
  • GSTM1
  • Lung cancer
  • p53

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

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