A discordance of the cytochrome P4502C19 genotype and phenotype in patients with advanced cancer

Aims To examine the relationship between cytochrome P450 2C19 (CYP2C19) gen otype and expressed metabolic activity in 16 patients with advanced metasta tic cancer. Methods Individual CYP2C19 genotypes were determined by PCR-based amplifica tion, followed by restriction fragment length analysis, and compared with o bserved CYP2C19 metabolic activity, as determined using the log hydroxylati on index of omeprazole. Results All 16 patients had an extensive metabolizer genotype. However, bas ed on the antimode in a distribution of log omeprazole hydroxylation indice s h-om healthy volunteers, four of the patients had a poor metabolizer phen otype 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 pat ient 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 genoty pe and expressed enzyme activity in cancer patients. Such a decrease in enz yme activity could have an impact on the efficacy and toxicity of chemother apeutic agents and other drugs, used in standard oncology practice.