A discordance of the cytochrome P450 2C19 genotype and phenotype in patients with advanced cancer

Br J Clin Pharmacol. 2000 May;49(5):485-8. doi: 10.1046/j.1365-2125.2000.00189.x.


Aims: To examine the relationship between cytochrome P450 2C19 (CYP2C19) genotype and expressed metabolic activity in 16 patients with advanced metastatic cancer.

Methods: Individual CYP2C19 genotypes were determined by PCR-based amplification, followed by restriction fragment length analysis, and compared with observed CYP2C19 metabolic activity, as determined using the log hydroxylation index of omeprazole.

Results: All 16 patients had an extensive metabolizer genotype. However, based on the antimode in a distribution of log omeprazole hydroxylation indices from healthy volunteers, four of the patients had a poor metabolizer phenotype and there was a general shift of the remaining 12 patients towards a slower metabolic phenotype. This suggests a reduction in metabolic activity for all patients relative to healthy volunteers. A careful analysis of patient medical records failed to reveal any drug interactions or other source for the observed discordance between genotype and phenotype.

Conclusions: There are no previous reports of a 'discordance' between genotype and expressed enzyme activity in cancer patients. Such a decrease in enzyme activity could have an impact on the efficacy and toxicity of chemotherapeutic agents and other drugs, used in standard oncology practice.

MeSH terms

  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / physiology
  • Female
  • Genotype
  • Humans
  • Hydroxylation
  • Male
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / physiology
  • Neoplasms / enzymology*
  • Omeprazole / metabolism
  • Phenotype


  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • CYP3A protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • Omeprazole