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Glutathione S-Transferase-µ (GSTM1) and - (GSTT1) Genotypes in the Etiology of Prostate Cancer¹

Departments of Biostatistics and Epidemiology [T. R. R., A. H. W., J. M. J., D. L. W.] and Urology [A. J. W., S. B. M.], University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

The glutathione S-transferases (GSTs) are involved in the metabolism of numerous potential prostate carcinogens. Common homozygous germ-line deletions exist in the genes that encode GST-|gm (GSTM1) and GST- (GSTT1) and preclude enzyme expression. To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer (CaP) etiology, we studied 237 incident CaP cases and 239 age- and race-matched controls. The probability of having CaP was increased in men who had nondeleted (functional) genotypes at GSTT1 (odds ratio, 1.83; 95% confidence interval, 1.19–2.80) but not GSTM1 (odds ratio, 1.07; 95% confidence interval, 0.74–1.55). No interaction of these genes in CaP etiology was observed. GST- is highly expressed in the prostate and can produce genotoxic effects upon exposure to specific carcinogens. These results suggest that GSTT1 is associated with CaP risk.

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