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Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer.
Holley, Sarah L; Rajagopal, Ramesh; Hoban, Paul R; Deakin, Mark; Fawole, Adeshina S; Elder, James B; Elder, Jackie; Smith, Victoria; Strange, Richard C; Fryer, Anthony A.
Afiliação
  • Holley SL; Human Genomics Research Group, Institute for Science and Technology in Medicine, Keele University School of Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 7QB, UK. s.l.holley@bemp.keele.ac.uk
Int J Oncol ; 28(1): 231-6, 2006 Jan.
Article em En | MEDLINE | ID: mdl-16328000
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< or =0.001). We identified no significant associations between the GSTP1(Ile105Val105) 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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Neoplasias Colorretais / Glutationa S-Transferase pi / Glutationa Transferase Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2006 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Neoplasias Colorretais / Glutationa S-Transferase pi / Glutationa Transferase Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2006 Tipo de documento: Article