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

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.

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