UNLABELLED: Glutathione S-transferases (GSTs) participate in the detoxification of chemotherapeutic agents. Genetic polymorphisms in GST genes (GSTP1 Ile105Val, copy-number variants of GSTM1 and GSTT1) that lead to diminished enzyme activity have been associated with increased chemotherapeutic treatment benefit in colorectal cancer patients. AIMS: We assessed the effect of genetic polymorphisms in GST genes on survival in colorectal cancer patients treated with adjuvant/palliative chemotherapy. As GSTs participate in the metabolism of platinum metabolites, we also assessed the association between genetic variants in GST genes and survival of colorectal cancer patients who received treatment with oxaliplatin. MATERIALS & METHODS: We followed 338 colorectal cancer patients treated with chemotherapy for a median of 36.4 months since treatment start. A total of 65 of the patients received treatment with oxaliplatin. Polymorphisms were genotyped by fluorescence-based melting curve analysis (GSTP1 Ile105Val), a relative quantification method (copy-number variants of GSTM1 and GSTT1), and PCR followed by gel electrophoresis (null/non-null genotypes for GSTM1 and GSTT1). Associations between genotypes and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: As hypothesized, GSTM1 copy number variant was inversely associated with survival in colorectal cancer patients treated with chemotherapy. Mortality was significantly reduced in patients with one GSTM1 copy (hazard ratio: 0.45, 95% CI: 0.23-0.90, p = 0.02) and nonsignificantly reduced in those with the null genotype (HR: 0.67, 95% CI: 0.35-1.27, p = 0.22) compared with carriers of two copies. Both GSTP1 genotype and GSTT1 genotype were not associated with survival. CONCLUSION: This is the first study to provide suggestive evidence for an effect of copy-number variation of GSTM1 on survival in colorectal cancer patients who received chemotherapy. Large studies are warranted to establish the impact of GST genotypes on treatment outcome in colorectal cancer patients.
UNLABELLED: Glutathione S-transferases (GSTs) participate in the detoxification of chemotherapeutic agents. Genetic polymorphisms in GST genes (GSTP1Ile105Val, copy-number variants of GSTM1 and GSTT1) that lead to diminished enzyme activity have been associated with increased chemotherapeutic treatment benefit in colorectal cancerpatients. AIMS: We assessed the effect of genetic polymorphisms in GST genes on survival in colorectal cancerpatients treated with adjuvant/palliative chemotherapy. As GSTs participate in the metabolism of platinum metabolites, we also assessed the association between genetic variants in GST genes and survival of colorectal cancerpatients who received treatment with oxaliplatin. MATERIALS & METHODS: We followed 338 colorectal cancerpatients treated with chemotherapy for a median of 36.4 months since treatment start. A total of 65 of the patients received treatment with oxaliplatin. Polymorphisms were genotyped by fluorescence-based melting curve analysis (GSTP1Ile105Val), a relative quantification method (copy-number variants of GSTM1 and GSTT1), and PCR followed by gel electrophoresis (null/non-null genotypes for GSTM1 and GSTT1). Associations between genotypes and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: As hypothesized, GSTM1 copy number variant was inversely associated with survival in colorectal cancerpatients treated with chemotherapy. Mortality was significantly reduced in patients with one GSTM1 copy (hazard ratio: 0.45, 95% CI: 0.23-0.90, p = 0.02) and nonsignificantly reduced in those with the null genotype (HR: 0.67, 95% CI: 0.35-1.27, p = 0.22) compared with carriers of two copies. Both GSTP1 genotype and GSTT1 genotype were not associated with survival. CONCLUSION: This is the first study to provide suggestive evidence for an effect of copy-number variation of GSTM1 on survival in colorectal cancerpatients who received chemotherapy. Large studies are warranted to establish the impact of GST genotypes on treatment outcome in colorectal cancerpatients.
Authors: Cassandra Johnson; Vernon S Pankratz; Ana I Velazquez; Jeremiah A Aakre; Charles L Loprinzi; Nathan P Staff; Anthony J Windebank; Ping Yang Journal: J Neurol Sci Date: 2015-01-05 Impact factor: 3.181
Authors: Niels F Jensen; Jan Stenvang; Mette K Beck; Barbora Hanáková; Kirstine C Belling; Khoa N Do; Birgitte Viuff; Sune B Nygård; Ramneek Gupta; Mads H Rasmussen; Line S Tarpgaard; Tine P Hansen; Eva Budinská; Per Pfeiffer; Fred Bosman; Sabine Tejpar; Arnaud Roth; Mauro Delorenzi; Claus L Andersen; Maria U Rømer; Nils Brünner; José M A Moreira Journal: Mol Oncol Date: 2015-02-24 Impact factor: 6.603
Authors: Zuzana Drobná; Luz Maria Del Razo; Gonzalo Garcia-Vargas; Blanca Sánchez-Ramírez; Carmen González-Horta; Lourdes Ballinas-Casarrubias; Dana Loomis; Miroslav Stýblo Journal: Chem Res Toxicol Date: 2011-12-21 Impact factor: 3.739