Cytochrome P4502C9 genotype in Southeast Anatolia and possible relation with some serum tumour markers and cytokines

Substrates for CYP2C9 include fluoxetine, phenytoin, warfarin, losartam and numerous nonsteroidal anti-inflammatory drugs. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino-acid residues 144 Arg/ Cys and 359 Ile/Leu of the CYP2C9 protein. Individuals homozygous for Leu35 9 have markedly diminished metabolic capacities for most CYP2C9 substrates, the frequency of this allele is, however, rather low. Consistently with th e modulation of enzyme activity by genetic and other factors, wide interind ividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. The polymorphic enzyme CYP2C9 takes part in the metabolism of alkylating agents and polycyclic aromatic hydrocarbons li ke benzo(a)pyrene, a carcinogen present in tobacco smoke. Although the impa ct of impaired enzyme activity in metabolism of carcinogens and procarcinog ens has not been fully defined, art association of CYP2C9 variant alleles t o DNA adduct levels in lung tissues as well as to lung cancer risk have bee n reported. In this study 64 healthy subjects (44M/22F) were analysed for CYP2C9 genoty pe with PCR-RFLP and for serum carcinoembryonic antigen (CEA), alpha -fetop rotein (AFP), CA 19-9, CA 15-3, ferritin, IL-6, IL-8 concentrations by chem iluminescence or electrochemiluminescence methods. CYP2C9*1 was found to be the most prevalent allele and CYP2C9*1/CYP2C9*1 wa s the most frequent genotype represented in 64% of the population in southe astern Anatolia (Gaziantep). Although slight differences in serum tumour ma rker and cytokine concentrations were observed for CYP2C9 genotypes the dif ferences were statistically insignificant (P > 0.05). This could be due to the complexity of the role of CYP2C9 in benzo(a)pyrene metabolism as well as from other contributing factors like interindividual variability of diverse enzymes participating in the same metabolic pathway , unequal expression of the variant alleles and differences in exposure to carcinogens. However, determination of CYP2C9 phenotypes in a larger group of subjects might clarify these slight differences.