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

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

M L Williams  1 , P Bhargava, I Cherrouk, J L Marshall, D A Flockhart, I W Wainer
Affiliations

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

M L Williams et al. Br J Clin Pharmacol. 2000 May.

Abstract

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.

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Figures

Figure 1
Figure 1
Frequency distribution and normit of the CYP2C19 metabolic phenotypes in (a) 77 healthy volunteers, as reported previously [1], and (b) 16 patients with advanced cancer.
See this image and copyright information in PMC

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