BACKGROUND: It has been reported that up to 80% of human cancers arise as a consequence of environmental exposure and host susceptibility factors. Environmental carcinogens are predominantly metabolized by the cytochrome P450 (CYP) superfamily of drug- or xenobiotic-metabolizing enzymes. Genetic variations in these enzymes affect individuals' susceptibility to carcinogens. AIM OF THE STUDY: The aim of this study was to evaluate the relationship between CYP2C19 polymorphism and susceptibility to these cancers by means of CYP2C19 genotyping among Turkish subjects. METHODS: DNAof subjects were isolated from leukocytes by high pure template preparation kit (Roche Diagnostics, GmbH, Mannheim, Germany) and genotypes were detected by LightCycler CYP2C19 Mutation Detection Kit by real-time PCR with LightCycler instrument (Roche Diagnostics, cat. no. 3113914). RESULTS: Being male was associated with a 3.5-fold (OR: 4.27, CI: 2.27-8.05) and 4.27-fold (OR: 3.50, CI: 1.948-6.301) risk for colorectal and gastric carcinoma, respectively. The CYP2C19*3 heterozygote genotype was not found in either gastric or colorectal carcinoma patients. Although the frequency of CYP2C19*2 heterozygote genotype is high in patients with gastric and colorectal carcinoma, it is not significantly associated with cancer (OR: 1.79, CI: 0.829-3.865 and OR: 1.998, CI: 0.961-4.154, respectively). CONCLUSION: Although the frequency of CYP2C19*2 heterozygote genotype is high in our patients with gastric and colorectal carcinoma, there is no the relationship between CYP2C19 polymorphism and susceptibility to these cancer.
BACKGROUND: It has been reported that up to 80% of humancancers arise as a consequence of environmental exposure and host susceptibility factors. Environmental carcinogens are predominantly metabolized by the cytochrome P450 (CYP) superfamily of drug- or xenobiotic-metabolizing enzymes. Genetic variations in these enzymes affect individuals' susceptibility to carcinogens. AIM OF THE STUDY: The aim of this study was to evaluate the relationship between CYP2C19 polymorphism and susceptibility to these cancers by means of CYP2C19 genotyping among Turkish subjects. METHODS: DNAof subjects were isolated from leukocytes by high pure template preparation kit (Roche Diagnostics, GmbH, Mannheim, Germany) and genotypes were detected by LightCycler CYP2C19 Mutation Detection Kit by real-time PCR with LightCycler instrument (Roche Diagnostics, cat. no. 3113914). RESULTS: Being male was associated with a 3.5-fold (OR: 4.27, CI: 2.27-8.05) and 4.27-fold (OR: 3.50, CI: 1.948-6.301) risk for colorectal and gastric carcinoma, respectively. The CYP2C19*3 heterozygote genotype was not found in either gastric or colorectal carcinomapatients. Although the frequency of CYP2C19*2 heterozygote genotype is high in patients with gastric and colorectal carcinoma, it is not significantly associated with cancer (OR: 1.79, CI: 0.829-3.865 and OR: 1.998, CI: 0.961-4.154, respectively). CONCLUSION: Although the frequency of CYP2C19*2 heterozygote genotype is high in our patients with gastric and colorectal carcinoma, there is no the relationship between CYP2C19 polymorphism and susceptibility to these cancer.
Authors: D R Nelson; L Koymans; T Kamataki; J J Stegeman; R Feyereisen; D J Waxman; M R Waterman; O Gotoh; M J Coon; R W Estabrook; I C Gunsalus; D W Nebert Journal: Pharmacogenetics Date: 1996-02