This Article Full Text 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 Sweeney, C. Articles by Vaughan, T. L. Search for Related Content PubMed PubMed Citation Articles by Sweeney, C. Articles by Vaughan, T. L.

Glutathione S-Transferase M1, T1, and P1 Polymorphisms as Risk Factors for Renal Cell Carcinoma: A Case-Control Study¹

Departments of Epidemiology [C. S., D. C. F., S. M. S., H. C., T. L. V.] and Environmental Health [D. L. E., H. C.], School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98195, and Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 [D. C. F., S. M. S., T. L. V.]

Renal cell carcinoma (RCC) has known environmental risk factors, notably smoking, and enzymes that biotransform carcinogens have high levels of activity in the kidney. However, a possible role of polymorphisms in these enzymes in RCC etiology has received little study. We investigated glutathione S-transferase (GST) polymorphisms in a population-based case-control study of RCC. Subjects completed a structured interview, and DNA was isolated from pathological material or buccal cells for 130 cases, and from blood for 505 controls. Genotypes for GSTM1 and GSTT1 were determined by multiplex PCR, and for GSTP1 by oligonucleotide ligation assay. The frequency of GSTM1 null genotype was 50.0% in cases and 50.5% in controls, with an adjusted odds ratio (OR) of 1.0 [95% confidence interval (CI), 0.6–1.6]. For GSTP1, the frequencies of genotypes AA, AG, and GG representing the Ile¹⁰⁴Val variant were: cases, 44.6%, 43.1%, and 12.3%; controls, 43.4%, 44.0%, and 12.6%; OR for AG and GG, 1.0 (95% CI, 0.6–1.6). An excess of the GSTT1 null genotype was observed in cases compared with controls, 28.6% versus 18.5% (OR, 1.9; 95% CI, 1.1–3.4). The association with GSTT1 was present among both smokers and nonsmokers, but was modified by body mass index, a recognized risk factor for RCC; among subjects in the lowest tertile of body mass index, the OR for GSTT1 null was 4.8 (95% CI, 1.8–13.0). The association between GSTT1 null and increased RCC risk in this population-based study suggests that activity of the GSTT1 enzyme protects against RCC. This contrasts with a recent report of reduced risk of RCC associated with GSTT1 null in a cohort of trichloroethene-exposed workers and suggests that specific chemical exposures alter the effect of GSTT1 on cancer risk.

This article has been cited by other articles:

				S. Karami, P. Boffetta, N. Rothman, R. J. Hung, T. Stewart, D. Zaridze, M. Navritalova, D. Mates, V. Janout, H. Kollarova, et al. Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms Carcinogenesis, August 1, 2008; 29(8): 1567 - 1571. [Abstract] [Full Text] [PDF]

				J. Shao, P. L. Stapleton, Y. S. Lin, and E. P. Gallagher Cytochrome P450 and Glutathione S-Transferase mRNA Expression in Human Fetal Liver Hematopoietic Stem Cells Drug Metab. Dispos., January 1, 2007; 35(1): 168 - 175. [Abstract] [Full Text] [PDF]

				N. K. Proia, G. M. Paszkiewicz, M. A. Sullivan Nasca, G. E. Franke, and J. L. Pauly Smoking and smokeless tobacco-associated human buccal cell mutations and their association with oral cancer--a review. Cancer Epidemiol. Biomarkers Prev., June 1, 2006; 15(6): 1061 - 1077. [Abstract] [Full Text] [PDF]

				B Yucesoy, V J Johnson, M L Kashon, K Fluharty, V Vallyathan, and M I Luster Lack of association between antioxidant gene polymorphisms and progressive massive fibrosis in coal miners Thorax, June 1, 2005; 60(6): 492 - 495. [Abstract] [Full Text] [PDF]

				L Buzio, G De Palma, P Mozzoni, M Tondel, C Buzio, I Franchini, O Axelson, and A Mutti Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals Occup. Environ. Med., October 1, 2003; 60(10): 789 - 793. [Abstract] [Full Text] [PDF]

				C. Sweeney, V. Nazar-Stewart, P. L. Stapleton, D. L. Eaton, and T. L. Vaughan Glutathione S-transferase M1, T1, and P1 Polymorphisms and Survival among Lung Cancer Patients Cancer Epidemiol. Biomarkers Prev., June 1, 2003; 12(6): 527 - 533. [Abstract] [Full Text] [PDF]

				J.-Q. He, J. Ruan, J. E. Connett, N. R. Anthonisen, P. D. Pare, and A. J. Sandford Antioxidant Gene Polymorphisms and Susceptibility to a Rapid Decline in Lung Function in Smokers Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 323 - 328. [Abstract] [Full Text] [PDF]

				S. Garte Metabolic Susceptibility Genes As Cancer Risk Factors: Time for a Reassessment? Cancer Epidemiol. Biomarkers Prev., December 1, 2001; 10(12): 1233 - 1237. [Abstract] [Full Text] [PDF]