Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymorphisms of the Glutathione-S Transferase (GST) family may influence the prognosis in lymphoma patients. We aimed to validate the impact of GSTT1 and GSTM1 deletions and of the GSTP1Ile105Val polymorphism on outcome and toxicity in 140 patients with advanced Hodgkin's lymphoma enrolled in the prospective multicenter HD2000-GISL trial, comparing ABVD, BEACOPP and CEC regimens. Carriers of the GSTP1Ile105Val polymorphism had a higher rate of grade 3-4 anemia following treatment. Overall, our study failed to validate GST genotyping as prognostic factor for progression-free survival (PFS). Only the small cohort of patients with an international prognostic score (IPS) >3 and undeleted GSTT1 and/or GSTM1, treated with ABVD had worse progression-free survival (PFS) (GSTT1 + vs GSTT1-: HR 5.02, 95% C.I., 1.16-21.8, p = 0.031, GSTM1 + /GSTT1 + vs GSTM1-and/or GSTT1-: HR 4.61, 95% C.I. 1.28- 16.6, p = 0.019, respectively). No differences were observed for patients treated with intensified regimens, as BEACOPP and CEC. In conclusion, the prognostic role of GST polymorphism, if at all, is limited to a small subgroup of patients treated with standard ABVD regimen.
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PMID:Role of glutathione-S-transferase (GST) polymorphisms in patients with advanced Hodgkin lymphoma: results from the HD2000 GISL trial. 2191 26

Glutathione S-transferases (GSTs) are postulated to be involved in the detoxification of potential carcinogens, and gene variation may alter susceptibility to lymphomas. Results from several previous epidemiologic studies have been inconsistent. Hence a meta-analysis was conducted to verify the role of GST genetic polymorphisms in lymphoma risk. Eleven trials involving 1626 patients and 2892 controls were analyzed. Pooled results showed that the GSTT1 null polymorphism might increase the risk of lymphoma (odds ratio [OR] 2.26, 95% confidence interval [CI] 1.20, 4.24; p = 0.01; random-effects model), whereas the impact of GSTM1 and GSTP1 Ile105Val polymorphisms was not significant. Subgroup analysis showed the GSTT1 null genotype to be a risk factor for non-Hodgkin lymphoma (NHL) (OR 2.75, 95% CI 1.17, 6.45; p = 0.02; random-effects model) but not for Hodgkin lymphoma (HL), and the effect remained evident in females (OR 1.43, 95% CI 1.04, 1.97; p = 0.03; I(2) = 41.0%, p for heterogeneity = 0.15; fixed-effects model). An effect of GSTM1 and GSTT1 double null genotype on lymphoma risk was also shown (OR 2.09, 95% CI 1.31, 3.33; p = 0.01; random-effects model). In conclusion, the GSTT1 null genotype appears to be associated with a modest increase in the risk of NHL, whereas the GSTM1 and GSTP1 Ile105Val polymorphisms are unrelated to lymphoma risk.
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PMID:Role of polymorphisms of GSTM1, GSTT1 and GSTP1 Ile105Val in Hodgkin and non-Hodgkin lymphoma risk: a Human Genome Epidemiology (HuGE) review. 2273 43

Glutathione-S-transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over-represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non-Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3'-UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age-matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77-22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.
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PMID:Positive association between a glutathione-S-transferase polymorphism and lymphoma in dogs. 2302 Feb 65