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Carcinogenesis, Vol 18, 641-644, Copyright © 1997 by Oxford University Press


ARTICLES

Identification of genetic polymorphisms at the glutathione S- transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer

LW Harries, MJ Stubbins, D Forman, GC Howard and CR Wolf
Imperial Cancer Research Fund, Ninewells Hospital and Medical School, Dundee, UK.

Two variant glutathione S-transferase cDNAs have been described at the GSTP1 locus, which differ by a single base pair (A-G) substitution at nucleotide 313 of the GSTP1 cDNA. This results in an amino acid substitution which alters the function of the enzyme. In this study, a novel PCR assay has been developed which demonstrates that these two variant cDNAs represent distinct GSTP1 alleles (GSTP1a and GSTP1b). In a study of individuals with different forms of cancer, the GSTP1b allele is found to be strongly associated with bladder cancer and testicular cancer. In controls 6.5% of individuals were homozygous for the GSTP1b allele. In bladder cancer cases, this rose to 19.7% [n = 71, odds ratio 3.6 (1.4-9.2), P = 0.006] and in testicular cancer to 18.7% [n = 155, odds ratio 3.3 (1.5-7.7), P = 0.002]. In addition, in prostate cancer a highly significant decrease in the frequency of the GSTP1a homozygotes was observed [control 51.0% versus 27.8% cancer cases, n = 36, odds ratio 0.4 (0.02-3.3), P = 0.008]. Increases in the frequency of GSTP1b homozygotes was also observed in lung cancer and chronic obstructive pulmonary disease. However, these were not statistically significant. No change in breast or colon cancer allele frequencies was observed.
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J. D. Brooks, V. G. Paton, and G. Vidanes
Potent Induction of Phase 2 Enzymes in Human Prostate Cells by Sulforaphane
Cancer Epidemiol. Biomarkers Prev., September 1, 2001; 10(9): 949 - 954.
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