Carcinogenesis, Vol 19, 275-280, Copyright © 1998 by Oxford University Press
MA Watson, RK Stewart, GB Smith, TE Massey and DA Bell
The association between glutathione S-transferase (GST) activity as
measured by 1-chloro-2,4-dinitrobenzene (CDNB) conjugation and genotype at
exon 5 and exon 6 of the human GSTP1 gene was investigated in normal lung
tissue obtained from 34 surgical patients. These samples were genotyped for
previously identified polymorphisms in exon 5 (Ile105Val) and exon 6
(Ala114Val) by PCR-RFLP and direct sequencing. GST enzyme activity was
significantly lower among individuals with the 105 Val allele. Homozygous
Ile/Ile samples (n = 18) had a mean cytosolic CDNB conjugating activity of
74.9 +/- 3.8 nmol/mg per min; heterozygotes (n = 13) had a mean specific
activity of 62.1 +/- 4.2 nmol/mg per min and homozygous Val/Val (n = 3) had
a mean specific activity of 52.5 +/- 4.5 nmol/mg per min. The CDNB
conjugating activity measured for the Ile/Ile genotype group was
significantly different from that observed in the Ile/Val group (P = 0.03),
and from Ile/Val and Val/Val genotypes combined (P = 0.009). Mean GST
activity values were consistently lower in individuals with genotypes
containing the 105 valine allele, regardless of smoking exposure. Genotypes
at codon 114 were also assessed but the mean GST activity was not
significantly lower in individuals with the 114 valine allele. A new
haplotype, present in two samples who were homozygous 105Ile and had a
114Val, was identified and proposed as GSTP1*D. Frequencies of the exon 5
and exon 6 polymorphisms were determined in samples obtained from
European-Americans, African- Americans and Taiwanese. The differences
observed were highly significant suggesting the possibility of GSTP1
genotype-associated, ethnic differences in cancer susceptibility and
chemotherapeutic response.
ARTICLES
Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution
Laboratory of Computational Biology and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
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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]
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R. M. Lunn, D. A. Bell, J. L. Mohler, and J. A. Taylor Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2) Carcinogenesis, September 1, 1999; 20(9): 1727 - 1731. [Abstract] [Full Text] [PDF]
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 T Ishii, T Matsuse, S Teramoto, H Matsui, M Miyao, T Hosoi, H Takahashi, Y Fukuchi, and Y Ouchi Glutathione S-transferase P1 (GSTP1) polymorphism in patients with chronic obstructive pulmonary disease Thorax, August 1, 1999; 54(8): 693 - 696. [Abstract] [Full Text]
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K. J. Helzlsouer, A. J. Alberg, H.-Y. Huang, S. C. Hoffman, P. T. Strickland, J. W. Brock, V. W. Burse, L. L. Needham, D. A. Bell, J. A. Lavigne, et al. Serum Concentrations of Organochlorine Compounds and the Subsequent Development of Breast Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 1999; 8(6): 525 - 532. [Abstract] [Full Text]
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X. Hu, C. Herzog, P. Zimniak, and S. V. Singh Differential Protection against Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA Damage in HepG2 Cells Stably Transfected with Allelic Variants of {{pi}} Class Human Glutathione S-Transferase Cancer Res., May 1, 1999; 59(10): 2358 - 2362. [Abstract] [Full Text] [PDF]
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M. Welfare, A. M. Adeokun, M. F. Bassendine, and A. K. Daly Polymorphisms in GSTP1, GSTM1, and GSTT1 and Susceptibility to Colorectal Cancer1 Cancer Epidemiol. Biomarkers Prev., April 1, 1999; 8(4): 289 - 292. [Abstract] [Full Text] [PDF]
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E. M. M. van Lieshout, H. M. J. Roelofs, S. Dekker, C. J. J. Mulder, T. Wobbes, J. B. M. J. Jansen, and W. H. M. Peters Polymorphic Expression of the Glutathione Polymorphic Expression of the Glutathione S-Transferase P1 Gene and Its Susceptibility to Barrett's Esophagus and Esophageal Carcinoma Cancer Res., February 1, 1999; 59(3): 586 - 589. [Abstract] [Full Text] [PDF]
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J. M. Allan, C. P. Wild, S. Rollinson, E. V. Willett, A. V. Moorman, G. J. Dovey, P. L. Roddam, E. Roman, R. A. Cartwright, and G. J. Morgan Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia PNAS, September 25, 2001; 98(20): 11592 - 11597. [Abstract] [Full Text] [PDF]
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