CYP2C19 polymorphisms in patients with gastric and colorectal carcinoma

  • L. Tamer
  • B. Ercan
  • S. Ercan
  • N. Ateş
  • C. Ateş
  • K. Öcal
  • M. Dirlik
  • S. Aydin
  • U. Atik
Research Article



It has been reported that up to 80% of human cancer 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.


DNA of 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).


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).


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.

Key Words

CYP2C19 polymorphism gastric and colorectal carcinomas 


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  1. 1.
    Saadat I, Saadat M. Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Lett, 2001;169:21–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Modugno F, Knoll C, Kanbour-Shakir A, Romkes M. A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat, 2003;82:191–197.PubMedCrossRefGoogle Scholar
  3. 3.
    Miller, JA, Miller EC. Some historical aspects of N-aryl carcinogens and their metabolic activation. Environ Health Perspect, 1983;49:3–12PubMedCrossRefGoogle Scholar
  4. 4.
    Nelson DR, Koymans L, Kamataki T, et al.. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics, 1996; 6:1–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Xie HG, Kim RB, Wood AJ, Stein CM: Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol, 2001;41:815–850PubMedCrossRefGoogle Scholar
  6. 6.
    Shi WX, Chen SQ. Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population. World J Gastroenterol, 2004;10:1961–1963.PubMedGoogle Scholar
  7. 7.
    Agundez JA. Cytochrome P450 gene polymorphism and cancer. Curr Drug Metab, 2004;5:211–224.PubMedCrossRefGoogle Scholar
  8. 8.
    Brockton N, Little J, Sharp L, Cotton SC. N-Acetyltransferase and colorectal cancer: a huge review. Am J Epidomiol 2000;151:846–881.Google Scholar
  9. 9.
    Rooney PH, Murray GI, Stevenson DA, Haites NE, Cassidy J, McLeod HL. Comparative genomic hybridization and chromosomal instability in solid tumours. Br J Cancer 1999;80:862–873.PubMedCrossRefGoogle Scholar
  10. 10.
    Howson CP, Hiyama T, Wynder EL. The decline in gastric cancer: epidemiology of an unplanned trium ph. Epidemiol Rev 1986;8:1–27.PubMedGoogle Scholar
  11. 11.
    Katoh T, Boissy R, Nagata N, et al. Inherited polymorphism in the N-acetyltransferase 1 (NAT1) and 2 (NAT2) genes and susceptibility to gastric and colorectal adenocarcinoma. Int J Cancer, 2000;85:46–49.PubMedCrossRefGoogle Scholar
  12. 12.
    Suzuki S, Muroishi Y, Nakanishi I, Oda Y. 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 2004;39:220–230.PubMedCrossRefGoogle Scholar
  13. 13.
    Tanaka E. Update: genetic polymorphism of drug metabolizing enzymes in humans. J Clin Pharm Ther, 1999;24: 323–329.PubMedCrossRefGoogle Scholar
  14. 14.
    Wadelius M, Autrup JL, Stubbins MJ, et al. Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. Pharmacogenetics, 1999;9: 333–340.PubMedCrossRefGoogle Scholar
  15. 15.
    Roddam PL, Rollinson S, Kane E, et al. Poor metabolizers at the cytochrome P450 2D6 and 2C19 loci are at increased risk of developing adult acute leukaemia. Pharmacogenetic 2000;10:605–615.CrossRefGoogle Scholar
  16. 16.
    Sachse C, Smith G, Wilkie MJ, et al. A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis, 2002;23: 1839–1849.PubMedCrossRefGoogle Scholar
  17. 17.
    Chau TK, Marakami S, Kawai B, Nasu K, Kubota T, Ohnishi A. Genotype analysis of the CYP2C19 gene in HCV-seropositive patients with cirrhosis and hepatocellular carcinoma. Life Sci, 2000;67:1719–1724.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • L. Tamer
    • 5
  • B. Ercan
    • 5
  • S. Ercan
    • 1
  • N. Ateş
    • 2
  • C. Ateş
    • 4
  • K. Öcal
    • 3
  • M. Dirlik
    • 3
  • S. Aydin
    • 3
  • U. Atik
    • 5
  1. 1.Department of BioistatisticsMersin UniversityTurkey
  2. 2.Department of Medical Biology and GeneticsMersin UniversityTurkey
  3. 3.Department of General SurgeryMersin UniversityTurkey
  4. 4.Department of Genernal SurgeryKocaeli UniversityTurkey
  5. 5.Department of BiochemistryMersin University, Medical FacultyMersinTurkey

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