두경부 편평세포암종에서 CYP1A1, GSTM1, GSTT1, GSTP1 유전자 다형성 및 p53 과발현

The Relationship between the Polymorphism of CYP1A1, GSTM1, GSTT1, GSTP1 and p53 Overexpression in Head and Neck Squamous Cell Carcinoma

  • 태경 (한양대학교 의과대학 이비인후과학교실) ;
  • 박혜경 (한양대학교 의과대학 이비인후과학교실) ;
  • 이승환 (한양대학교 의과대학 이비인후과학교실) ;
  • 김경래 (한양대학교 의과대학 이비인후과학교실) ;
  • 이형석 (한양대학교 의과대학 이비인후과학교실)
  • Tae Kyung (Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University) ;
  • Park Hye-Kyung (Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University) ;
  • Lee Seung-Hwan (Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University) ;
  • Kim Kyung-Rae (Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University) ;
  • Lee Hyung-Seok (Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University)
  • 발행 : 2003.11.01

초록

Background and Objectives: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione S-transferase(GST) have been reported to be associated with risks to the smoking-related human cancers. Inactivation of tumor suppressor genes like p53 playa key role in tumor progression. The purpose of this study is to demonstrate an association between p53 overexpression and the prevalence of the genetic polymorphisms of CYP1A1 and GSTs in Korean head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The polymorphisms of CYPIA1 and GSTs were analyzed by PCR and PCR-RFLP in 98 Korean head and neck squamous cell carcinoma patients. The expression of p53 was analyzed by immunohistochemistry with anti-p53 Ab (DO7). Results: Overexpression of p53 detected in 45.9% of HNSCC. The odds ratio for p53 overexpression in GSTM1(-), GSTT1(-), GSTP1(val/val) and CYP1A1(val/val) were 1.53, 1.83, 1.17 and 1.47, respectively. Among the combined genotypes, the odds ratio of the CYP1A1 val/val, GSTM1 (-), CYP1A1 val/val, GSTT1(-), and CYP1A1 val/val, GSTT1(-) were 2.0, 2.34 and 4.68, respectively. Conclusion: Based on our results, it might be suggested that p53 overexpression is slightly increased in GSTM1(-), GSTT1(-), GSTP1 val/val, CYP1A1 val/val genotypes. The further study is needed to evaluate the relationship and mechanism between the p53 overexpression and the specific CYP1A1 and GSTs genotypes.

키워드

참고문헌

  1. Matthis C, Bockmuhl U, Jahnke V, et al : Polymorphism in cytochrome P450, CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers : studies in upper aerodigestive tract cancers. Pharmacogenetics. 1998 ; 8 : 91-100
  2. Shin CS, Ahn KS, Tae K, et al : Genetic susceptibility of CYP1A1 and GSTM1 to the risk for Korean head and neck squamous cell carcinoma patients. Korean J Otolaryngol. 1999 ; 42 : 202-208
  3. Board PJ : Biochemical genetics of glutathione S-transferase in man. Am J Hum Genet. 1981 ; 33 : 36-43
  4. Board P, Coggan M, Johnston P, et al : Genetic heterogeneity of the human glutathione transferase : a complex of gene families. Pharmacol. 1990 ; 48 : 357-369
  5. Philip L, Sabina NS, Qing R, et al : p53, but not p16 mutations in oral squamous cell caricnomas are associated with specific CYP1A1 and GSTM1 polymorphic genotypes and patient tobacco use. Carcinogenesis. 1998 ; 19 : 509-514 https://doi.org/10.1093/carcin/19.3.509
  6. Dude Ophuis MB, van Kieshout EM, Roelofs HM, et al : Glutathione S-transferase M1 and T1 and cytochrome P4501A1 polymorphisms in relation to the risk for benign and malignant head and neck lesions. Cancer. 1998 : 81 : 936-943
  7. Nakachi K, Imai K, Hayashi S, et al : Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. Cancer Res. 1991 ; 51 : 5177-5180
  8. Alexandrie AK, Sundberg MI, Seidegard J, et al : Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1 : A study on host factors in relation to age at onset, gender and histological cancer types. Carcinogenesis. 1994 ; 15 : 1785-1790 https://doi.org/10.1093/carcin/15.9.1785
  9. Ko KM, Ahn KS, Tea K, et al : Genetic polymorphism of cytochrome P4501Al exon 7 and glutathione S-transferase M1 in the head and neck squamous cell carcinoma patients. Korean J Otolaryngol. 1999 ; 42 : 1405-1412
  10. Watson MA, Stewart RK, Smith BJ, et al : Human glutathione S-transferase P1 polymorphisms relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis (Lond.). 1995 ; 16 : 2125-2128
  11. Harris AL : Mutant p53-the commonest genetic abnormality in human cancer? J pathol. 1990 ; 162 : 5-6
  12. Kawajiri K, Eguchi H, Nakachi K, et al : Association of CYPIA1 germ line polymorphisms with mutations of the p53 gene in lung cancer. Cancer Res. 1996 ; 56 : 72-76
  13. Jeffrey E, McWilliams, Adam JE, Tomasz MB, et al : Genetic polymorphisms in head and neck cancer risk. Head Neck. 2000 ; 22 :609-617 https://doi.org/10.1002/1097-0347(200009)22:6<609::AID-HED10>3.0.CO;2-L
  14. Mark Welfare, A. Monesola Adeokun, Margaret F. Bassendine, Ann K. Daly: Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer. Cancer Epidemiology, Biomarkers & Prevention. 1999 ; 8 : 289-292
  15. Hayashi S, Watanabe J, Nakachi K, Kawajiri K : Genetic linkage of lung cancer-associated Msp I polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P4501 IAl gene. J Biochem. 1991 ; 110 : 407-411
  16. Kihara M, Noda K : Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYPIAI and GSTM1 gene polymorphisms in a Japanes population. Carcinogenesis. 1995 ; 16 : 2331-2336 https://doi.org/10.1093/carcin/16.10.2331
  17. Comstock KE, Sanderson BJ, Claflin G, Heuner WD : GSTM1 gene deletion determined by polymerase chain reaction. Nucleic Acids Res. 1990 ; 18 : 3670
  18. Warwick A, Sarhauis P, Redman G, et al : Theta class glutathione S-transferase GSTTI genotypes and susceptibility to cervical neoplasia: Interactions with GSTMl, CYP2D6 and smoking. Carcinogenesis. 1994 ; 15 : 2841-2845 https://doi.org/10.1093/carcin/15.12.2841
  19. Matthias C, Bockmuhl U, Jahnke V, et al : The glutathione Stransferase GSTP1 polymorphism : effects on susceptubility to oral/pharyngeal and laryngeal carcinomas. Pharmacogenetics. 1998;8 :1-6 https://doi.org/10.1097/00008571-199802000-00001
  20. Rebbeck TR : Molecula epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTTI in cancer susceptibility. Cancer Epidemiol. Biomark. Prevo 1997 ; 6 : 733-743
  21. Park JY, Stimson P. Schantz, Jordan C. Stem, et al : Association between glutathione Saransferase IT genetic polymorphisms and oral canper risk. Pharmarcogenetics. 1999 ; 9 : 497-504
  22. Oude Ophuis MB, van Kieshout EM, Roelofs HM, et al : Glutathione S-transferase M1 and T1 and cytochrome P4501A1 polymorphism in relation to the risk for benign and malignant head and neck lesions. Cancer. 1998 ; 82 (5) : 936-943 https://doi.org/10.1002/(SICI)1097-0142(19980301)82:5<936::AID-CNCR20>3.0.CO;2-0
  23. Choi G, Lee JS, Yoo DH, et al : p53 mutation patterns in primary head and neck squamous cell carcinomas and their metastatic neck nodes. Korean J Otolaryngol. 1998 ; 41 : 906-912
  24. Field JK, Spandidos DA, Malliri A : Elevated p53 expression correlates with a history of heavy smoking in squamous cell carcinoma ofhead and neck. Br J Cancer. 1991 ; 64 : 573-581 https://doi.org/10.1038/bjc.1991.352
  25. Boyle JO, Hakim J, Koch W, et al : The incidence of p53 mutations increases with progression of head and neck cancer. Cancer Res. 1993 ; 53 : 4477-4480
  26. Kihara M, Kubota A, Fumkawa M, Kimura H : GSTM1 gene polymorphism as a possible marker for susceptibility to head and neck cancers among Japanese smokers. Cancer Letters. 1997 ; 12 : 257-262
  27. Greenbalt MS, Bennett WP,Hollstein M, Harris CC : Mutations in the p53 tumor suppressor gene ; Clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994 ; 54 : 4855-4878