Carcinogenesis, Vol 18, 641-644, Copyright © 1997 by Oxford University Press
LW Harries, MJ Stubbins, D Forman, GC Howard and CR Wolf
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.
ARTICLES
Identification of genetic polymorphisms at the glutathione S- transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer
Imperial Cancer Research Fund, Ninewells Hospital and Medical School, Dundee, UK.
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