BACKGROUND: The glutathione S-transferases (GSTs) are a group of multifunctional enzymes that catalyze the conjugation of glutathione with a variety of electrophilic compounds, including cytotoxic agents. A significant percentage of normal individuals exhibit genetic polymorphism with a homozygous deletion (null genotype) of the genes, leading to absence of the enzyme. METHODS: In the present study we analyzed GSTM1 and GSTT1 polymorphisms in the genomic DNA isolated from peripheral blood of patients with ovarian cancer treated with chemotherapy (paclitaxel and cisplatinum) after cytoreductive surgery and assessed its correlation with the clinical outcome of these patients. The median follow-up for the patients was 30 months. RESULTS: The estimated 3-year survival rate was 59.8% for all patients and 20.8% for carriers of GSTM1-wt/GSTT1-wt (wt indicates wild type) genotype combination (37.7% for GSTM1-wt alone) compared with 83.1% for non-GSTM1-wt/GSTT1-wt genotype carriers (100% for GSTM1-null). The mean survival time was significantly better in patients who are carriers of the GSTM1-null genotype (40.5 vs. 33.5; P=0.006) or carriers of non-GSTM1-wt/ GSTT1-wt genotypes (55.4 vs. 30.7; P=0.009). The progression-free interval was more favorable for GSTM1-null carriers (41.9 vs. 27.4; P=0.024). CONCLUSION: The study suggests that characterization of the drug-metabolizing genetic individual profile can be of great interest in clinical oncology. It can define the optimal chemotherapy for each patient, improve the efficiency, and reduce the incidence of drug toxicity and poor drug responses.
BACKGROUND: The glutathione S-transferases (GSTs) are a group of multifunctional enzymes that catalyze the conjugation of glutathione with a variety of electrophilic compounds, including cytotoxic agents. A significant percentage of normal individuals exhibit genetic polymorphism with a homozygous deletion (null genotype) of the genes, leading to absence of the enzyme. METHODS: In the present study we analyzed GSTM1 and GSTT1 polymorphisms in the genomic DNA isolated from peripheral blood of patients with ovarian cancer treated with chemotherapy (paclitaxel and cisplatinum) after cytoreductive surgery and assessed its correlation with the clinical outcome of these patients. The median follow-up for the patients was 30 months. RESULTS: The estimated 3-year survival rate was 59.8% for all patients and 20.8% for carriers of GSTM1-wt/GSTT1-wt (wt indicates wild type) genotype combination (37.7% for GSTM1-wt alone) compared with 83.1% for non-GSTM1-wt/GSTT1-wt genotype carriers (100% for GSTM1-null). The mean survival time was significantly better in patients who are carriers of the GSTM1-null genotype (40.5 vs. 33.5; P=0.006) or carriers of non-GSTM1-wt/ GSTT1-wt genotypes (55.4 vs. 30.7; P=0.009). The progression-free interval was more favorable for GSTM1-null carriers (41.9 vs. 27.4; P=0.024). CONCLUSION: The study suggests that characterization of the drug-metabolizing genetic individual profile can be of great interest in clinical oncology. It can define the optimal chemotherapy for each patient, improve the efficiency, and reduce the incidence of drug toxicity and poor drug responses.
Authors: Elaine Cristina Morari; Andre Bacellar Costa Lima; Natassia Elena Bufalo; Janaina Luisa Leite; Fabiana Granja; Laura Sterian Ward Journal: J Cancer Res Clin Oncol Date: 2006-05-19 Impact factor: 4.553
Authors: Ann M Moyer; Zhifu Sun; Anthony J Batzler; Liang Li; Daniel J Schaid; Ping Yang; Richard M Weinshilboum Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-03-03 Impact factor: 4.254
Authors: Prema Peethambaram; Brooke L Fridley; Robert A Vierkant; Melissa C Larson; Kimberly R Kalli; Elaine A Elliott; Ann L Oberg; Kristin L White; David N Rider; Gary L Keeney; Julie M Cunningham; Lynn C Hartmann; Ellen L Goode Journal: Int J Mol Epidemiol Genet Date: 2011-05-02
Authors: R Stephanie Huang; Shiwei Duan; Sunita J Shukla; Emily O Kistner; Tyson A Clark; Tina X Chen; Anthony C Schweitzer; John E Blume; M Eileen Dolan Journal: Am J Hum Genet Date: 2007-08-01 Impact factor: 11.025