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

  • Published : 2007.12.31

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.

Keywords

References

  1. Agundez JA. (2004) Cytochrome P450 gene polymorphism and cancer. Curr. Drug Metab. 5, 211-224 https://doi.org/10.2174/1389200043335621
  2. Chau TK, Marakami S, Kawai B, Nasu K, Kubota T, Ohnishi A. (2000) Genotype analysis of the CYP2C19 gene in HCV-seropositive patients with cirrhosis and hepatocellular carcinoma. Life Sci. 67, 1719-1724 https://doi.org/10.1016/S0024-3205(00)00757-8
  3. De Morais SM, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA. (1994) Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol. Pharmacol. 46, 594-598
  4. De Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA. (1994) The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J. Biol. Chem. 269, 15419-15422
  5. Gao C, Takezaki T, Wu J, Li Z, Wang J, Ding J, Liu Y, Hu X, Xu T, Tajima K, Sugimura H. (2002) Interaction between cytochrome P-450 2E1 polymorphisms and environmental factors with risk of esophageal and stomach cancers in Chinese. Cancer Epidemiol. Biomarkers Prev. 11, 29-34
  6. Ishizaki T, Sohn DR, Kobayashi K, Chiba K, Lee KH, Shin SG, Andersson T, Reg?dh CG, Lou YC, Zhang Y, Dahl ML, Bertilsson L. (1994) Interethnic differences in omeprazole metabolism in the two S-mephenytoin hydroxylation phenotypes studied in Caucasians and Orientals. Ther. Drug Monit. 16, 21-215 https://doi.org/10.1097/00007691-199404000-00018
  7. Kamataki T, Fujita K, Nakayama K, Yamazaki Y, Miyamoto M, Ariyoshi N. (2002) Role of human cytochrome P450 (CYP) in the metabolic activation of nitrosamine derivatives: application of genetically engineered Salmonella expressing human CYP. Drug Metab. Rev. 34, 667-676 https://doi.org/10.1081/DMR-120005668
  8. Klose TS, Blaisdell JA, Goldstein JA (1999) Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. J. Biochem.Mol. Toxicol. 13, 289-295 https://doi.org/10.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-N
  9. Roddam PL, Rollinson S, Kane E, Roman E, Moorman A, Cartwright R, Morgan GJ. (2000) Poor metabolizers at the cytochrome P450 2D6 and 2C19 loci are at increased risk of developing adult acute leukaemia. Pharmacogenetics 10, 605-615 https://doi.org/10.1097/00008571-200010000-00004
  10. Sachse C, Smith G, Wilkie MJ, Barrett JH, Waxman R, Sullivan F, Forman D, Bishop DT, Wolf CR. (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23, 1839-1849 https://doi.org/10.1093/carcin/23.11.1839
  11. Shi WX, Chen SQ. (2004) Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population. World J. Gastroenterol. 10, 1961-1963
  12. Sugimoto M, Furuta T, Shirai N, Nakamura A, Kajimura M, Sugimura H, Hishida A, Ishizaki T. (2005) Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection. Aliment. Pharmacol. Ther. 22, 1033-1040 https://doi.org/10.1111/j.1365-2036.2005.02678.x
  13. Suzuki S, Muroishi Y, Nakanishi I, Oda Y. (2004) Relationship between genetic polymorphisms of drug-metabolizing enzymes (CYP1A1, CYP2E1, GSTM1, and NAT2), drinking habits, histological subtypes, and p53 gene point mutations in Japanese patients with gastric cancer. J. Gastroenterol. 39, 220- 230 https://doi.org/10.1007/s00535-003-1281-x
  14. Tsuneoka Y, Fukushima K, Matsuo Y, Ichikawa Y, Watanabe Y. (1996) Genotype analysis of the CYP2C19 gene in the Japanese population. Life Sci. 59, 1711-1715 https://doi.org/10.1016/S0024-3205(96)00507-3
  15. Wadelius M, Autrup JL, Stubbins MJ, Andersson SO, Johansson JE, Wadelius C, Wolf CR, Autrup H, Rane A. (1999) Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. Pharmacogenetics 9, 333-340 https://doi.org/10.1097/00008571-199906000-00008
  16. Xiao ZS, Goldstein JA, Xie HG, Blaisdell J, Wang W, Jiang CH, Yan FX, He N, Huang SL, Xu ZH, Zhou HH. (1997) Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. J. Pharmacol. Exp. Ther. 281, 604-609
  17. Xie HG, Kim RB, Wood AJ, Stein CM. (2001) Molecular basis of ethnic differences in drug disposition and response. Annu. Rev. Pharmacol. Toxicol. 41, 815-850 https://doi.org/10.1146/annurev.pharmtox.41.1.815
  18. Xie HG, Kim RB, Stein CM, Wilkinson GR, Wood AJ. (1999) Genetic polymorphism of (S)-mephenytoin 4?hydroxylation in populations of African descent. Br. J. Clin Pharmacol. 48, 402-408 https://doi.org/10.1046/j.1365-2125.1999.00009.x
  19. Xing D, Tan W, Lin D. (2003) Genetic polymorphisms and susceptibility to esophageal cancer among Chinese population. Oncol. Rep. 10, 1615-1623
  20. Yokose T, Doy M, Kakiki M, Horie T, Matsuzaki Y, Mukai K. (1998) Expression of cytochrome P450 3A4 in foveolar epithelium with intestinal metaplasia of the human stomach. Jpn. J. Cancer Res. 89, 1028-1032