Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer

  • Authors:
    • Sarah L. Holley
    • Ramesh Rajagopal
    • Paul R. Hoban
    • Mark Deakin
    • Adeshina S. Fawole
    • James B. Elder
    • Jackie Elder
    • Victoria Smith
    • Richard C. Strange
    • Anthony A. Fryer
  • View Affiliations

  • Published online on: January 1, 2006     https://doi.org/10.3892/ijo.28.1.231
  • Pages: 231-236
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Abstract

Glutathione S-transferase (GST) enzymes catalyse the detoxification of by-products of reactive oxygen species and are thus important in cellular defence mechanisms. The GSTs are polymorphic with allelic variants encoding isoforms with functional differences. GST polymorphism has been associated with susceptibility and clinical outcome in patients with cancer. In this retrospective cohort, we have investigated associations between common GSTM1, GSTM3 and GSTP1 polymorphisms with factors known to influence clinical out-come and patient survival in colorectal cancer. Significant linkage disequilibrium was demonstrated between GSTM1 and GSTM3 alleles (P≤0.001). We identified no significant associations between the GSTP1Ile105Val105 polymorphism and any clinical outcome parameters or patient survival. However significant associations were demonstrated with mu class GSTs. Those patients who were GSTM1 null presented less frequently with poorly-differentiated tumours (P=0.038). Furthermore, patients who were GSTM3 AA were less likely to present with advanced stage tumours (T-stage, P=0.036 and Dukes' classifications, P=0.012) or distant metastases (P=0.017) when examined alone. Upon further examination of the effect of linkage disequilibrium, we found that, in GSTM1 null individuals, GSTM3 AA (compared with other GSTM3 genotypes combined) had longer disease-free survival (HR=0.54, 95% CI 0.30-0.98, P=0.044). Thus, the GSTM3 AA genotype is associated with improved prognosis especially in those with GSTM1 null. Our findings suggest that the GST mu gene cluster mediates tumour characteristics and survival in patients with colorectal cancer.

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January 2006
Volume 28 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Holley SL, Rajagopal R, Hoban PR, Deakin M, Fawole AS, Elder JB, Elder J, Smith V, Strange RC, Fryer AA, Fryer AA, et al: Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer. Int J Oncol 28: 231-236, 2006
APA
Holley, S.L., Rajagopal, R., Hoban, P.R., Deakin, M., Fawole, A.S., Elder, J.B. ... Fryer, A.A. (2006). Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer. International Journal of Oncology, 28, 231-236. https://doi.org/10.3892/ijo.28.1.231
MLA
Holley, S. L., Rajagopal, R., Hoban, P. R., Deakin, M., Fawole, A. S., Elder, J. B., Elder, J., Smith, V., Strange, R. C., Fryer, A. A."Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer". International Journal of Oncology 28.1 (2006): 231-236.
Chicago
Holley, S. L., Rajagopal, R., Hoban, P. R., Deakin, M., Fawole, A. S., Elder, J. B., Elder, J., Smith, V., Strange, R. C., Fryer, A. A."Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer". International Journal of Oncology 28, no. 1 (2006): 231-236. https://doi.org/10.3892/ijo.28.1.231