This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anttila, S. Articles by Ketterer, B. Search for Related Content PubMed PubMed Citation Articles by Anttila, S. Articles by Ketterer, B.

Pulmonary Expression of Glutathione S-Transferase M3 in Lung Cancer Patients: Association with GSTM1 Polymorphism, Smoking, and Asbestos Exposure¹

Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland [S. A., L. L., A. H., E. E., A. K., T. N., H. V.]; Biomedical Research Centre, Ninewells Hospital, Dundee DD1 9SY, Scotland [J. D. H.]; and Department of Biochemistry and Molecular Biology, University College of London, London W1P 6DB, England [B. K.]

To characterize the relative roles of glutathione S-transferases (GST) M1 and M3 in the susceptibility to lung cancer, the pulmonary expression of GSTM3 was quantified immunochemically and related to the GSTM1 genotype in 100 lung cancer patients. Among active smokers and recent ex-smokers (for 6 years or less), parenchymal GSTM3 expression was lower in patients with a homozygous GSTM1 null genotype than in those who were GSTM1 positive and had similar smoking habits (P < 0.001 and P = 0.004, respectively). However, in long-term ex-smokers (for 15 years or longer) GSTM3 was not affected by the GSTM1 genotype. Among active smokers and recent ex-smokers who were homozygous GSTM1 null, those with a definite or probable exposure to asbestos expressed GSTM3 at significantly higher levels than those for whom it was unlikely (P = 0.04). A similar effect of the homozygous GSTM1 null genotype on GSTM3 expression was not detected in the bronchial epithelium when GSTM3 was visualized immunohistochemically. Different mechanisms may result in an increased risk of either squamous cell or adenocarcinomas in patients with the homozygous GSTM1 null genotype. Low expression of GSTM3 due to smoking in the parenchymal lung of GSTM1 null individuals can theoretically favor the development of adenocarcinoma. Our data indicated a predominance of this tumor type in patients with low expression of GSTM3.

¹ Supported by The Finnish Academy of Sciences and The Finnish Foundation for Cancer Research, Helsinki, Finland.

² To whom requests for reprints should be addressed.

Received 2/16/95. Accepted 5/25/95.

This article has been cited by other articles:

				P Vineis, F Veglia, S Garte, C Malaveille, G Matullo, A Dunning, M Peluso, L Airoldi, K Overvad, O Raaschou-Nielsen, et al. Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers Ann. Onc., July 1, 2007; 18(7): 1230 - 1242. [Abstract] [Full Text] [PDF]

				M. Unal, M. Guven, K. Devranoglu, A. Ozaydin, B. Batar, N. Tamcelik, E. Eroglu Gorgun, D. Ucar, and A. Sarici Glutathione S transferase M1 and T1 genetic polymorphisms are related to the risk of primary open-angle glaucoma: a study in a Turkish population Br. J. Ophthalmol., April 1, 2007; 91(4): 527 - 530. [Abstract] [Full Text] [PDF]

				X. Liu, M. R. Campbell, G. S. Pittman, E. C. Faulkner, M. A. Watson, and D. A. Bell Expression-Based Discovery of Variation in the Human Glutathione S-Transferase M3 Promoter and Functional Analysis in a Glioma Cell Line Using Allele-Specific Chromatin Immunoprecipitation Cancer Res., January 1, 2005; 65(1): 99 - 104. [Abstract] [Full Text] [PDF]

				A. Ahmadi, P. Jonsson, U. Flodin, and P. Soderkvist Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy Toxicology and Industrial Health, July 1, 2002; 18(6): 289 - 296. [Abstract] [PDF]

				I. Stucker, P. Boffetta, S. Antilla, S. Benhamou, A. Hirvonen, S. London, and E. Taioli Lack of Interaction between Asbestos Exposure and Glutathione S-Transferase M1 and T1 Genotypes in Lung Carcinogenesis Cancer Epidemiol. Biomarkers Prev., December 1, 2001; 10(12): 1253 - 1258. [Abstract] [Full Text] [PDF]

				A. IZZOTTI, C. CARTIGLIA, J. LEWTAS, and S. DE FLORA Increased DNA alterations in atherosclerotic lesions of individuals lacking the GSTM1 genotype FASEB J, March 1, 2001; 15(3): 752 - 757. [Abstract] [Full Text] [PDF]

				M. H. WILSON, P. J. GRANT, L. J. HARDIE, and C. P. WILD Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction FASEB J, April 1, 2000; 14(5): 791 - 796. [Abstract] [Full Text]

				E. L. Crawford, S. A. Khuder, S. J. Durham, M. Frampton, M. Utell, W. G. Thilly, D. A. Weaver, W. J. Ferencak, C. A. Jennings, J. R. Hammersley, et al. Normal Bronchial Epithelial Cell Expression of Glutathione Transferase P1, Glutathione Transferase M3, and Glutathione Peroxidase Is Low in Subjects with Bronchogenic Carcinoma Cancer Res., March 1, 2000; 60(6): 1609 - 1618. [Abstract] [Full Text]

				S.-M. Hou, D. Ryberg, S. Falt, A. Deverill, T. Tefre, A.-L. Borresen, A. Haugen, and B. Lambert GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients Carcinogenesis, January 1, 2000; 21(1): 49 - 54. [Abstract] [Full Text] [PDF]

				R. S. Houlston Glutathione S-Transferase M1 Status and Lung Cancer Risk: A Meta-Analysis Cancer Epidemiol. Biomarkers Prev., August 1, 1999; 8(8): 675 - 682. [Abstract] [Full Text]

				C. Lai and P. G. Shields The Role of Interindividual Variation in Human Carcinogenesis J. Nutr., February 1, 1999; 129(2): 552 - 552. [Abstract] [Full Text] [PDF]