Polymorphisms of GSTP1 and related genes and prostate cancer risk

Tomasz (Tom) Beer, A. J. Evans, K. M. Hough, B. A. Lowe, J. E. McWilliams, W. D. Henner

    Research output: Contribution to journalArticle

    35 Citations (Scopus)

    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 X2 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.

    Original languageEnglish (US)
    Pages (from-to)22-27
    Number of pages6
    JournalProstate Cancer and Prostatic Diseases
    Volume5
    Issue number1
    DOIs
    StatePublished - Jan 1 2002

    Fingerprint

    Glutathione Transferase
    Prostatic Neoplasms
    Prostate
    Genes
    Adenocarcinoma
    Down-Regulation
    Logistic Models
    Genotype
    Prostatic Intraepithelial Neoplasia
    Cytochrome P-450 CYP1A1
    Population Control
    Amino Acid Substitution
    Carcinogens
    Case-Control Studies
    Carcinogenesis
    Nucleotides
    Odds Ratio
    Binding Sites
    Demography
    Polymerase Chain Reaction

    Keywords

    • GSTP1
    • Polymorphism
    • Prostate cancer
    • Risk

    ASJC Scopus subject areas

    • Oncology
    • Urology
    • Cancer Research

    Cite this

    Beer, T. T., Evans, A. J., Hough, K. M., Lowe, B. A., McWilliams, J. E., & Henner, W. D. (2002). Polymorphisms of GSTP1 and related genes and prostate cancer risk. Prostate Cancer and Prostatic Diseases, 5(1), 22-27. https://doi.org/10.1038/sj.pcan.4500549

    Polymorphisms of GSTP1 and related genes and prostate cancer risk. / Beer, Tomasz (Tom); Evans, A. J.; Hough, K. M.; Lowe, B. A.; McWilliams, J. E.; Henner, W. D.

    In: Prostate Cancer and Prostatic Diseases, Vol. 5, No. 1, 01.01.2002, p. 22-27.

    Research output: Contribution to journalArticle

    Beer, TT, Evans, AJ, Hough, KM, Lowe, BA, McWilliams, JE & Henner, WD 2002, 'Polymorphisms of GSTP1 and related genes and prostate cancer risk', Prostate Cancer and Prostatic Diseases, vol. 5, no. 1, pp. 22-27. https://doi.org/10.1038/sj.pcan.4500549
    Beer, Tomasz (Tom) ; Evans, A. J. ; Hough, K. M. ; Lowe, B. A. ; McWilliams, J. E. ; Henner, W. D. / Polymorphisms of GSTP1 and related genes and prostate cancer risk. In: Prostate Cancer and Prostatic Diseases. 2002 ; Vol. 5, No. 1. pp. 22-27.
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