| 2016 | Do Variants in GSTs Modify the Association between Traffic Air Pollution and Asthma in Adolescence? | Int J Mol Sci | Polymorphisms in genes involved in the oxidative stress response may partially explain the documented heterogeneous associations between traffic-related air pollution (TRAP) exposure and asthma and allergies in children. We investigated whether the GSTT1, GSTM1 and GSTP1 gene polymorphisms modified the associations between TRAP exposure during the first year of life and asthma, wheeze and hay fever in adolescence. We used a birth cohort of 620 high risk infants from the Melbourne Atopy Cohort Study. TRAP exposure during the first year of life was defined as the cumulative length of major roads within 150 m of each participant's residence during the first year of life. Wheeze, asthma and hay fever were measured at ages 12 (n = 370) and 18 (n = 434) years. The associations and interactions with glutathione S-transferases (GST s) were investigated using regression models. Overall, there was no relationship between TRAP exposure during the first year of life and current asthma, wheeze and hay fever at ages 12 or 18 years. However, in GSTT1 null carriers, every 100 m increase in cumulative lengths of major road exposure during the first year of life was associated with a 2.31-fold increased risk of wheeze and a 2.15-fold increased risk of asthma at 12 years. TRAP is associated with some respiratory outcomes in carriers of genetic polymorphisms in oxidative stress metabolism genes. |
| 2010 | Glutathione-S-transferase genotypes influence the risk of chemotherapy-related toxicities and prognosis in Korean patients with diffuse large B-cell lymphoma. | Cancer Genet Cytogenet | Polymorphisms in detoxification enzymes of the glutathione S-transferase (GST) family are associated with treatment response, resistance, and drug-related toxicity, all of which affect final clinical outcome. In this study, we investigated the influence of the genetic polymorphisms GSTM1, GSTT1, and GSTP1 on treatment response in 94 Korean patients with de novo diffuse large B-cell lymphoma, who had received rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) as a front-line regimen. Deletions of the GSTM1 and GSTT1 genes were detected using a multiplex polymerase chain reaction technique, and the functional GSTP1 polymorphism, Ile(105)Val, was genotyped using the TaqMan assay. The treatment response rate did not differ according to GST polymorphisms. Patients with the GSTT1-null genotype, however, showed more frequent grade III-IV chemotherapy-related toxicities, including leukocytopenia [odds ratio (OR)=3.1; 95% confidence interval (95%CI), 1.2-8.0; P=0.025], fever (OR=5.3; 95% CI, 1.4-19.7; P=0.009), and mucositis (OR=4.6; 95% CI, 1.4-15.1; P=0.012). Patients with the GSTM1/T1 double-null genotype had more grade III-IV thrombocytopenia (OR=7.8; 95% CI, 1.5-41.1; P=0.002) compared to those with other genotypes. In male patients, the GSTM1/T1 double-null genotype was associated with a shorter event-free survival period (P=0.02). This study suggests that GSTT1 deletion may significantly increase the risk of drug-related toxicity after R-CHOP chemotherapy in patients with DLBCL, and is associated with worse prognosis in males. |