Abstract
Lung cancer is closely associated with cigarette smoking. Aromatic hydrocarbons in smoke, including benzo[n]pyrene, first require metabolic activation by Phase I enzymes, cytochrome P450, to their ultimate forms, and these activated forms are then subjected to detoxification by Phase II enzymes, especially glutathione S‐transferases. Thus, genetically determined susceptibility to lung cancer may depend on the metabolic balance between Phase I and Phase II enzymes. In this study, we identified individuals genetically at high risk of lung cancer in terms of polymorphisms of the P450IA1 gene and GST1 gene. The relative risk of individuals with a combination of the genotypes of both a homozygous rare allele of the P450IA1 gene and the nulled GST1 gene was remarkably high at 5.8 for lung cancer and 9.1 for squamous cell carcinoma compared with other combinations of genotypes.
Keywords: Key words, Human, Lung cancer, Glutathione S‐transferase, Genetic polymorphism — P450
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REFERENCES
- 1. ) Omenn , G. S.Risk assessment, pharmacogenetics, and ecogenetics . Banbury Rep. , 16 , 3 – 13 ( 1988. ). [Google Scholar]
- 2. ) Kellermann , G. , Shaw , C. R. and Luyten‐Kellermann , M.Aryl hydrocarbon hydroxylase inducibility and bronchogenie carcinoma . N. Engl. J. Med. , 289 , 934 – 937 ( 1973. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Ayesh , R. , Idle , J. R. , Ritchie , J. C. , Crothers , M. J. and Hetzel , M. R.Metabolic oxidation phenotypes as markers for susceptibility to lung cancer . Nature , 312 , 169 – 170 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 4. ) McLemore , T. L. , Adelberg , S. , Liu , M. C. , McMahon , N. A. , Yu , S. J. , Hubbard , W. C. , Czerwinski , M. , Wood , T. G. , Storeng , R. , Lubet , R. A. , Eggleston , J. C. , Boyd , M. R. and Hines , R. N.Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke‐induced gene expression in normal lung tissue and for pulmonary carcinomas . J. Natl. Cancer Inst. , 82 , 1333 – 1339 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Kawajiri , K. , Nakachi , K. , Imai , K. , Yoshii , A. , Shinoda , N. and Watanabe , J.Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene . FEBS Lett. , 263 , 131 – 133 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Nakachi , K. , Imai , K. , Hayashi , S.‐L. , Watanabe , J. and Kawajiri , K.Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose . Cancer Res. , 51 , 5177 – 5180 ( 1991. ). [PubMed] [Google Scholar]
- 7. ) Hayashi , S.‐L , Watanabe , J. , Nakachi , K. and Kawajiri , K.Genetic linkage of lung cancer‐associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene . J. Biochem. , 110 , 407 – 411 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Mannervik , B. and Danielson , U. H.Glutathione transferases: structure and catalytic activity . CRC Crit. Biochem. , 23 , 281 – 337 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Seidegard , J. , Vorachek , W. R. , Pero , R. W. and Pearson , W. R.Hereditary differences in the expression of the human glutathione transferase active on frans‐stilbene oxide are due to a gene deletion . Proc. Natl. Acad. Sci. USA , 85 , 7293 – 7297 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Seidegard , J. , Pero , R. W. , Miller , D. G. and Beattie , E. J.A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer . Carcinogenesis , 7 , 751 – 753 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Seidegård , J. , Pero , R. W. , Markowitz , M. M. , Roush , G. , Miller , D. G. and Beattie , E. J.Isoenzymes of glutathione transferase (class Mu) as a marker for the susceptibility to lung cancer: a follow up study . Carcinogenesis , 11 , 33 – 36 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Hayashi , S.‐L , Watanabe , J. , Nakachi , K. and Kawajiri , K.PCR detection of an A/G polymorphism within exon 7 of the CYP1A1 gene . Nucleic Acids Res. , 18 , 7194 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Comstock , K. E. , Sanderson , J. S. , Claflin , G. and Henner , W. D.GST1 gene deletion determined by polymerase chain reaction . Nucleic Acids Res. , 18 , 3670 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. ) Groppi , A. , Coutelle , C. , Fleury , B. , Iron , A. , Begueret , J. and Couzigous , P.Glutathione S‐transferase class μ in French alcoholic cirrhotic patients . Hum. Genet , 87 , 628 – 630 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Laisney , V. , Van Cong , N. , Gross , M. S. and Frezal , J.Human genes for glutathione S‐transferases . Hum. Genet. , 68 , 221 – 227 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Harada , S. , Abei , M. , Tanaka , N. , Agarwal , D. P. and Goedde , H. W.Liver glutathione S‐transferase polymorphism in Japanese and its pharmacogenetic importance . Hum. Genet. , 75 , 322 – 325 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Hussey , A. J. , Hayes , J. D. and Beckett , G. J.The polymorphic expression of neutral glutathione S‐transferase in human mononuclear leukocytes as measured by specific radio immunoassay . Biochem. Pharmacol. , 36 , 4013 – 4015 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Zhong , S. , Howie , A. F. , Ketterer , B. , Taylor , J. , Hayes , J. D. , Beckett , G. J. , Wathen , C. G. , Wolf , C. R. and Spurr , N. K.Glutathione S‐transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility . Carcinogenesis , 12 , 1533 – 1537 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Breslow , N. E. and Day , N. E. “ Statistical Methods in Cancer Research. Vol. I. The Analysis of Case‐control Studies ,” IARC Scientific Publications No. 32 , pp. 73 – 78 ( 1980. ). International Agency for Research on Cancer; , Lyon . [PubMed] [Google Scholar]
- 20. ) Tefre , T. , Ryberg , Haugen , A. , Nebert , D. W. , Skaug , V. , Brøgger , A. and Børresen , A.‐L.Human CYP1A1 (cytochrome P1450) gene: lack of association between the Msp I restriction fragment length polymorphism and incidence of lung cancer in a Norwegian population . Pharmacogenetics , 1 , 20 – 25 ( 1991. ). [DOI] [PubMed] [Google Scholar]