High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu-class glutathione S-transferase genes

Jpn J Cancer Res. 1992 Aug;83(8):866-70. doi: 10.1111/j.1349-7006.1992.tb01992.x.


Lung cancer is closely associated with cigarette smoking. Aromatic hydrocarbons in smoke, including benzo[a]pyrene, first require metabolic activation by Phase I enzymes, cytochrome P450, to their ultimate forms, and these activated forms are then subjected to detoxification by Phase II enzymes, especially glutathione S-transferases. Thus, genetically determined susceptibility to lung cancer may depend on the metabolic balance between Phase I and Phase II enzymes. In this study, we identified individuals genetically at high risk of lung cancer in terms of polymorphisms of the P450IA1 gene and GST1 gene. The relative risk of individuals with a combination of the genotypes of both a homozygous rare allele of the P450IA1 gene and the nulled GST1 gene was remarkably high at 5.8 for lung cancer and 9.1 for squamous cell carcinoma compared with other combinations of genotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / genetics
  • Amino Acid Sequence
  • Base Sequence
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / genetics
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA / blood
  • DNA / genetics
  • DNA / isolation & purification
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • Disease Susceptibility
  • Genotype
  • Glutathione Transferase / genetics*
  • Isoenzymes / genetics*
  • Lung Neoplasms / blood
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Molecular Sequence Data
  • Neoplasms / blood
  • Neoplasms / genetics
  • Oligonucleotide Probes
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic
  • Reference Values


  • DNA, Neoplasm
  • Isoenzymes
  • Oligonucleotide Probes
  • DNA
  • Cytochrome P-450 Enzyme System
  • Glutathione Transferase