title: Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy.
abstract: GSTM1 (glutathione S-transferase mu 1) and GSTT1 (glutathione S-transferase theta 1) are critical enzymes for detoxification of endogenous and environmental carcinogens. Constitutive GST gene polymorphisms may be associated with increased risk for cancer development. We made an explorative study of a Brazilian population with malignant glioma to determine whether GSTM1 and GSTT1 genetic polymorphisms influence the response to intranasal administration of perillyl alcohol and the survival rate. Patients were stratified into groups according to clinical presentation, tumor classification, and tumor location. Circulating DNA was extracted from blood plasma or serum, and genotypes were detected by multiplex PCR. The cohort included 95 patients with recurrent malignant glioma included in a Phase I/II clinical trial with perillyl alcohol and 100 matched healthy control subjects. GSTM1 frequency was similar in patients with glioma (44%) and healthy controls (54%), but GSTT1 deletion was found in 11.5% patients, contrasting with 36% in controls. A longer survival rate was associated with a lack of GSTM1 deletion (31 weeks) and a deletion for GSTT1 (28 weeks). A poor survival rate was associated with GSTM1 deletion (23 weeks) and with a lack of a GSTT1 deletion (19 weeks). A significantly lower frequency of GSTT1 deletion in glioma patients compared to healthy controls indicates that GSTT1 deletion may exert a protective role against gliomagenesis, influence therapeutic response to intranasal perillyl alcohol treatment, and increase overall survival, especially considering tumor topography.
authors.affiliation: Laboratório de Controle da Expressão Gênica, Instituto de Biofísica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: M M
authors.initials: MM
authors.lastname: Silva
authors.forename: C O
authors.initials: CO
authors.lastname: Da Fonseca
authors.forename: R
authors.initials: R
authors.lastname: Moura-Neto
authors.forename: J F
authors.initials: JF
authors.lastname: Carvalho
authors.forename: T
authors.initials: T
authors.lastname: Quirico-Santos
authors.forename: M G
authors.initials: MG
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D003710:Demography; D005091:Exons / Q000235:genetics; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000401:mortality*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D039821:Monoterpenes / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D005982:Glutathione Transferase; D039821:Monoterpenes; D016159:Tumor Suppressor Protein p53; C032208:perillyl alcohol; C413545:glutathione S-transferase T1