Association of gastric cancer with cytochrome P450 2C19 single-nucleotide polymorphisms in Koreans

Abstract

Cytochrome P450 2C19 (CYP2C19) is a clinically important enzyme involved in the metabolism of therapeutic drugs, including (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals are characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2 -5% of Caucasians, but in 18 -23% of Asians. To clarify the association between CYP2C19 polymorphisms and gastric cancer in Koreans, we investigated CYP2C19 genotypes (CYP2C19*1, *2, and *3) in 109 patients with gastric cancer and 211 controls. Normal (CYP2C19*1) and defective alleles were detected with polymerase chain reaction/restriction enzyme analysis. CYP2C19 has three hereditary genotypes: homozygous EM, with high enzymatic activity; heterozygous EM, with moderate enzymatic activity; and PM, with no enzyme activity. We found that CYP2C19 heterozygous EM is more closely associated with gastric cancer than is homozygous EM. Because the CYP2C19 genotype varies in Koreans, a genotyping test is desirable to prevent gastropathy recurrence in patients before their doses of omeprazole are reduced during maintenance therapy.

Evaluating the Association of Genetic Polymorphism of Cytochrome p450 (CYP2C9*3) in Gastric Cancer Using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP)

“…Its role in esophageal, antral, and duodenal carcinogenesis and tumor proliferation is well documented. The heterozygous extensive metabolizer (EM) variant is more closely associated with GC compared to the homozygous EM ones [20]. Gastrointestinal tract (GIT) bleeding is more commonly observed in patients on dual therapy with non-steroidal antiinflammatory drugs (NSAID) and warfarin [21].…”