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 Nazar-Stewart, V. Articles by Weiss, N. S. Search for Related Content PubMed PubMed Citation Articles by Nazar-Stewart, V. Articles by Weiss, N. S.

The Glutathione S-Transferase µ Polymorphism as a Marker for Susceptibility to Lung Carcinoma¹

Departments of Epidemiology [V. N. S., E. W., Z. T. L., N. S. W.], Medicine and Genetics [A. G. M., S. K. H.], and Environmental Health [D. L. E., P. S.], University of Washington, Seattle 98195, and the Fred Hutchinson Cancer Research Center, Seattle 98194 [V. N. S., E. W., N. S. W.], Washington

Glutathione S-transferase (GST) enzymes detoxify carcinogens in tobacco smoke. Interindividual variation in GST function may be related to differences in risk for smoking-related cancer. Leukocytes from 50% of Caucasians lack GST activity toward trans-stilbene oxide (TSO), due to a deletion of the gene for the GST-µ enzyme. Presence of GST-TSO activity in leukocytes has been associated with low risk for lung cancer among cigarette smokers. We sought to determine whether GST activity in lung tissue is determined by the same gene polymorphism and whether it is associated with risk for lung cancer.

Subjects were cigarette smokers, identified at the time of lung resection or autopsy in Seattle hospitals. Uninvolved lung tissue was obtained from 35 patients with lung carcinoma and 43 control patients and assayed for GST-µ activity with TSO, for the presence of the GST-µ gene product with an immunological assay, and for the GST-µ gene with Southern blotting. Mailed questionnaires were used to collect information on subjects' smoking histories and exposures which might alter enzyme activity.

Interindividual results from the three assays correlated well. Smokers with high GST-TSO enzyme activity present in their lung tissue had a lower risk for lung carcinoma than did smokers with no or low activity (relative risk = 0.30; 95% confidence interval, 0.11–0.79), as did smokers with GST-µ antigen identified in lung tissue versus those with no antigen (relative risk = 0.30; 95% confidence interval, 0.11–0.79). Smokers with both maternal and paternal copies of GST-µ DNA (n = 7) had a lower cancer risk than smokers lacking GST-µ DNA (n = 30; relative risk = 0.35; 95% confidence interval, 0.06–2.10). High GST-µ activity appeared to be associated with a greater decrease in lung cancer risk among 38 heavy cigarette smokers (relative risk = 0.15; 95% confidence interval, 0.03–0.64) than among 38 light smokers (relative risk = 0.61; 95% confidence interval, 0.14–2.60).

Presence or absence and number of copies of the GST-µ gene appear to determine activity of the GST-µ enzyme in lung. Smokers with the GST-µ enzyme have approximately one-third of the risk for lung carcinoma of smokers without the enzyme.

¹ Supported by Grants R35 CA39779 and T32 CA09168 from the National Cancer Institute, NIH Grant ES-05780, and a Dana Foundation Grant in Ecogenetics and Environmental Health.

² To whom requests for reprints should be addressed, at Department of Epidemiology SC-36, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195.

Received 11/17/92. Accepted 3/11/93.

This article has been cited by other articles:

				C. Carlsten, G. S. Sagoo, A. J. Frodsham, W. Burke, and J. P. T. Higgins Glutathione S-Transferase M1 (GSTM1) Polymorphisms and Lung Cancer: A Literature-based Systematic HuGE Review and Meta-Analysis Am. J. Epidemiol., April 1, 2008; 167(7): 759 - 774. [Abstract] [Full Text] [PDF]

				M. E. Kushman, S. L. Kabler, S. Ahmad, J. Doehmer, C. S. Morrow, and A. J. Townsend Protective Efficacy of hGSTM1-1 against B[a]P and (+)- or ( )-B[a]P-7,8-Dihydrodiol Cytotoxicity, Mutagenicity, and Macromolecular Adducts in V79 Cells Coexpressing hCYP1A1 Toxicol. Sci., September 1, 2007; 99(1): 51 - 57. [Abstract] [Full Text] [PDF]

				M.L. Cote, S.L.R. Kardia, A.S. Wenzlaff, S.J. Land, and A.G. Schwartz Combinations of glutathione S-transferase genotypes and risk of early-onset lung cancer in Caucasians and African Americans: a population-based study Carcinogenesis, April 1, 2005; 26(4): 811 - 819. [Abstract] [Full Text] [PDF]

				D. Palli, G. Masala, P. Vineis, S. Garte, C. Saieva, V. Krogh, S. Panico, R. Tumino, A. Munnia, E. Riboli, et al. Biomarkers of dietary intake of micronutrients modulate DNA adduct levels in healthy adults Carcinogenesis, April 1, 2003; 24(4): 739 - 746. [Abstract] [Full Text] [PDF]

				G E Goodman Lung cancer * 1: Prevention of lung cancer Thorax, November 1, 2002; 57(11): 994 - 999. [Abstract] [Full Text] [PDF]

				S. Benhamou, W. J. Lee, A.-K. Alexandrie, P. Boffetta, C. Bouchardy, D. Butkiewicz, J. Brockmoller, M. L. Clapper, A. Daly, V. Dolzan, et al. Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk Carcinogenesis, August 1, 2002; 23(8): 1343 - 1350. [Abstract] [Full Text] [PDF]

				S. Garte, L. Gaspari, A.-K. Alexandrie, C. Ambrosone, H. Autrup, J. L. Autrup, H. Baranova, L. Bathum, S. Benhamou, P. Boffetta, et al. Metabolic Gene Polymorphism Frequencies in Control Populations Cancer Epidemiol. Biomarkers Prev., December 1, 2001; 10(12): 1239 - 1248. [Abstract] [Full Text] [PDF]

				J. G. Ford, Y. Li, M. M. O'Sullivan, R. Demopoulos, S. Garte, E. Taioli, and P. W. Brandt-Rauf Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans Carcinogenesis, November 1, 2000; 21(11): 1971 - 1975. [Abstract] [Full Text] [PDF]

				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]

				M. Stanulla, M. Schrappe, A. M. Brechlin, M. Zimmermann, and K. Welte Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study Blood, February 15, 2000; 95(4): 1222 - 1228. [Abstract] [Full Text] [PDF]

				L.J. Hardie, J.A. Briggs, L.A. Davidson, J.M. Allan, R.F.G.J. King, G.I. Williams, and C.P. Wild The effect of hOGG1 and glutathione peroxidase I genotypes and 3p chromosomal loss on 8-hydroxydeoxyguanosine levels in lung cancer Carcinogenesis, February 1, 2000; 21(2): 167 - 172. [Abstract] [Full Text] [PDF]

				J.-J. Yim, G. Y. Park, C.-T. Lee, Y. W. Kim, S. K. Han, Y.-S. Shim, and C.-G. Yoo Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1 Thorax, February 1, 2000; 55(2): 121 - 125. [Abstract] [Full Text]

				M. Rojas, I. Cascorbi, K. Alexandrov, E. Kriek, G. Auburtin, L. Mayer, A. Kopp-Schneider, I. Roots, and H. Bartsch Modulation of benzo[a]pyrene diolepoxide-DNA adduct levels in human white blood cells by CYP1A1, GSTM1 and GSTT1 polymorphism Carcinogenesis, January 1, 2000; 21(1): 35 - 41. [Abstract] [Full Text] [PDF]

				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. K. Stewart, G. B.J. Smith, P. J. Donnelly, K. R. Reid, D. Petsikas, A.A. Conlan, and T. E. Massey Glutathione S-transferase-catalyzed conjugation of bioactivated aflatoxin B1 in human lung: differential cellular distribution and lack of significance of the GSTM1 genetic polymorphism Carcinogenesis, October 1, 1999; 20(10): 1971 - 1977. [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]

				V. Nazar-Stewart, T. L. Vaughan, R. D. Burt, C. Chen, M. Berwick, and G. M. Swanson Glutathione S-Transferase M1 and Susceptibility to Nasopharyngeal Carcinoma Cancer Epidemiol. Biomarkers Prev., June 1, 1999; 8(6): 547 - 551. [Abstract] [Full Text]

				C. Chen and W. Nirunsuksiri Decreased expression of glutathione S-transferase M1 in HPV16-transfected human cervical keratinocytes in culture Carcinogenesis, April 1, 1999; 20(4): 699 - 703. [Abstract] [Full Text] [PDF]

				C.-L. Chen, Q. Liu, C.-H. Pui, G. K. Rivera, J. T. Sandlund, R. Ribeiro, W. E. Evans, and M. V. Relling Higher Frequency of Glutathione S-Transferase Deletions in Black Children With Acute Lymphoblastic Leukemia Blood, March 1, 1997; 89(5): 1701 - 1707. [Abstract] [Full Text] [PDF]