Abstract
Glutathione S-transferase P1 (GSTP1) is markedly downregulated in prostate cancer and prostatic intraepithelial neoplasia compared to normal prostate tissue. Downregulation of GSTP1 may, therefore, be an early event in prostate carcinogenesis. An A→G polymorphism at nucleotide 313 results in an amino acid substitution (Ile105Val) in the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. In a study of 36 prostate cancer patients, Harries et al. reported that the Ile/Ile genotype is associated with a decreased risk of prostate cancer (odds ratio 0.4 (0.17–0.82)). We sought to confirm this finding and to examine the impact of this polymorphism together with several related polymorphisms implicated as risk factors for carcinogen-associated malignancies. One hundred and seventeen patients with prostate adenocarcinoma and 183 population-based controls were recruited to this case–control study. Genotyping of the GSTP1 (Ile105Val), GSTM1 (null), GSTT1 (null) and CYP1A1 (Ile462Val) genes was performed using polymerase chain reaction (PCR) based techniques on DNA prepared from peripheral blood. A questionnaire was used to collect demographic information from each subject. Cases were significantly older (P<0.0001) and had significantly greater family history of prostate cancer (P<0.0001), confirming known risk factors for this disease. By χ2 analysis, none of the genotype distributions varied among cases and controls. Using a logistic regression model to control for known risk factors we were also unable to demonstrate a significant association with prostate cancer for any of the polymorphisms tested. This population fails to identify a relationship between the above polymorphisms and prostate adenocarcinoma.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 4 print issues and online access
$259.00 per year
only $64.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cannon L, Bishop DT, Skolnick M. . Genetic epidemiology of prostate cancer in the Utah Mormon genealogy. Cancer Surv 1982 1: 47–69.
Steinberg GD et al.. Family history and the risk of prostate cancer. Prostate 1990 17: 337–347.
Spitz MR et al.. Familial patterns of prostate cancer: a case-control analysis. J Urol 1991 146: 1305–1307.
Bastacky SI et al.. Pathological features of hereditary prostate cancer. J Urol 1995 153: 3 Pt 2 987–992.
Tsuchida S, Sato K. . Glutathione transferases and cancer. Crit Rev Biochem Mol Biol 1992 27: 337–384.
De Marzo AM, Marchi VL, Epstein JI, Nelson WG. . Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol 1999 155: 1985–1992.
Lee WH et al.. Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci USA 1994 91: 11733–11737.
Cookson MS, Reuter VE, Linkov I, Fair WR. . Glutathione S-transferase PI (GST-pi) class expression by immunohistochemistry in benign and malignant prostate tissue. J Urol 1997 157: 673–676.
Moskaluk CA et al.. Immunohistochemical expression of pi-class glutathione S-transferase is down-regulated in adenocarcinoma of the prostate. Cancer 1997 79: 1595–1599.
Lee WH, Isaacs WB, Bova GS, Nelson WG. . CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate cancer biomarker. Cancer Epidemiol Biomarkers Prev 1997 6: 443–450.
Brooks JD et al.. CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev 1998 7: 531–536.
Millar DS et al.. Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer. Oncogene. 1999 18: 1313–1324.
Singal R, van Wert J, Bashambu M. . Cytosine methylation represses glutathione S-transferase P1 (GSTP1) gene expression in human prostate cancer cells. Cancer Res 2001 61: 4820–4826.
De Marzo AM, Nelson WG, Meeker AK, Coffey DS. . Stem cell features of benign and malignant prostate epithelial cells. J Urol 1998 160: 6 Pt 2 2381–2392.
DeWeese TL, Hruszkewycz AM, Marnett LJ. . Oxidative stress in chemoprevention trials. Urology 2001 57: Suppl 137–140.
Nelson WG, De Marzo AM, DeWeese TL. . The molecular pathogenesis of prostate cancer: implications for prostate cancer prevention. Urology 2001 57: Suppl 39–45.
Nelson CP et al.. Protection against 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine cytotoxicity and DNA adduct formation in human prostate by glutathione S-transferase P1. Cancer Res 2001 61: 103–109.
Ali-Osman F et al.. Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 1997 272: 10004–10012.
Sundberg K et al.. Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons. Carcinogenesis 1998 19: 433–436.
Harries LW et al.. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 1997 18: 641–644.
Kote-Jarai Z et al.. Relationship between glutathione S-transferase M1, P1 and T1 polymorphisms and early onset prostate cancer. Pharmacogenetics 2001 11: 325–330.
Gsur A et al.. Polymorphisms of glutathione-S-transferase genes (GSTP1, GSTM1 and GSTT1) and prostate-cancer risk. Int J Cancer 2001 95: 152–155.
Autrup JL et al.. Glutathione S-transferases as risk factors in prostate cancer. Eur J Cancer Prev 1999 8: 525–532.
Shepard TF et al.. No association between the I105V polymorphism of the glutathione S-transferase P1 gene (GSTP1) and prostate cancer risk: a prospective study. Cancer Epidemiol Biomarkers Prev 2000 9: 1267–1268.
Steinhoff C et al.. Glutathione transferase isozyme genotypes in patients with prostate and bladder carcinoma. Arch Toxicol 2000 74: 521–526.
Board PG. . Biochemical genetics of glutathione-S-transferase in man. Am J Hum Genet 1981 33: 36–43.
Seidegard J, Guthenberg C, Pero RW, Mannervik B. . The trans-stilbene oxide-active glutathione transferase in human mononuclear leucocytes is identical with the hepatic glutathione transferase mu. Biochem J 1987 246: 783–785.
Seidegard J, Pero RW, Miller DG, Beattie EJ. . A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. Carcinogenesis 1986 7: 751–753.
Murata M et al.. Cytochrome P4501A1 and glutathione S-transferase M1 genotypes as risk factors for prostate cancer in Japan. Jpn J Clin Oncol 1998 28: 657–660.
Rebbeck TR et al.. Glutathione S-transferase-mu (GSTM1) and -theta (GSTT1) genotypes in the etiology of prostate cancer. Cancer Epidemiol Biomarkers Prev 1999 8: 4 Pt 1 283–287.
Wadelius M et al.. Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. Pharmacogenetics 1999 9: 333–340.
Pemble S et al.. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 1994 300: 271–276.
Autrup JL et al.. Glutathione S-transferases as risk factors in prostate cancer. Eur J Cancer Prev 1999 8: 525–532.
Murata M et al.. Genetic polymorphisms in cytochrome P450 (CYP) 1A1, CYP1A2, CYP2E1, glutathione S-transferase (GST) M1 and GSTT1 and susceptibility to prostate cancer in the Japanese population. Cancer Lett 2001 165: 171–177.
Kawajiri K et al.. The CYP1A1 gene and cancer susceptibility. Crit Rev Oncol Hematol 1993 14: 77–87.
Kawasaki ES. . Sample preparation from blood, cells, and other fluids. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds). PCR Protocols: A Guide to Methods and Application. Academic Press: San Diego 1990 146–152.
Comstock KE, Sanderson BJ, Claflin G, Henner WD. . GST1 gene deletion determined by polymerase chain reaction. Nucleic Acids Res 1990 18: 3670.
Schlesselman J. . Case–Control Studies: Design, Conduct, Analysis Oxford University Press: New York 1982
Thompson MW, McInnes RR, Willard HF, Thompson JS. . Thompson & Thompson Genetics in Medicine5th ed. W.B. Saunders Co: Philadelphia 1991
Pienta KJ, Esper PS. . Risk factors for prostate cancer. Ann Intern Med 1993 118: 793–803.
Adler V et al.. Regulation of JNK signaling by GSTp. EMBO J 1999 18: 1321–1334.
Kauvar LM, Morgan AS, Sanderson PE, Henner WD. . Glutathione based approaches to improving cancer treatment. Chem Biol Interact 1998 111/112: 225–238.
Acknowledgements
We would like to thank Dr Emily Harris for her suggestions and Dr Gary Sexton for statistical advice. This work was supported in part by grant 1R01 CA 72792-01 from the National Institutes of Health.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Beer, T., Evans, A., Hough, K. et al. Polymorphisms of GSTP1 and related genes and prostate cancer risk. Prostate Cancer Prostatic Dis 5, 22–27 (2002). https://doi.org/10.1038/sj.pcan.4500549
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.pcan.4500549
Keywords
This article is cited by
-
Exploring putative molecular mechanisms of human pyruvate kinase enzyme deficiency and its role in resistance against Plasmodium falciparum malaria
Interdisciplinary Sciences: Computational Life Sciences (2014)
-
Association of GSTT1 gene polymorphisms with the risk of prostate cancer: an updating meta-analysis
Tumor Biology (2013)
-
Quantitative synthesis of the association between the cytochrome P450 1A1 Ile462Val polymorphism and prostate cancer risk
Tumor Biology (2013)
-
Association of CYP1A1 polymorphisms with prostate cancer risk: an updated meta-analysis
Molecular Biology Reports (2012)
-
Examination of polymorphic glutathione S-transferase (GST) genes, tobacco smoking and prostate cancer risk among Men of African Descent: A case-control study
BMC Cancer (2009)