RGD Reference Report - Increased risk for therapy-associated hematologic malignancies in patients with carcinoma of the breast and combined homozygous gene deletions of glutathione transferases M1 and T1. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Increased risk for therapy-associated hematologic malignancies in patients with carcinoma of the breast and combined homozygous gene deletions of glutathione transferases M1 and T1.

Authors: Haase, D  Binder, C  Bunger, J  Fonatsch, C  Streubel, B  Schnittger, S  Griesinger, F  Westphal, G  Schoch, C  Knopp, A  Berkovicz, D  Krieger, O  Wormann, B  Hilgers, R  Hallier, E  Schulz, T 
Citation: Haase D, etal., Leuk Res. 2002 Mar;26(3):249-54.
RGD ID: 10450857
Pubmed: PMID:11792413   (View Abstract at PubMed)

The most serious long-term complications of anti-tumor therapy are secondary malignancies. Parameters which might allow an estimation of the individual risk to develop a therapy-induced neoplasia are urgently needed. We examined whether the genotypes of the glutathione S-transferases (GST) M1 and T1, which metabolize various cytostatic drugs, as well as reactive oxygen species, influence the risk for secondary neoplasia. In a retrospective study, we analyzed peripheral blood lymphocyte or bone marrow DNA samples from 213 patients with acute myeloid leukemia (AML) and 128 with myelodysplastic syndromes (MDS) 44 of whom suffered from therapy-associated AML/MDS. The control group consisted of 239 healthy individuals with comparable composition as to race and sex. GSTM1 and GSTT1 were analyzed by multiplex PCR. Comparison between patients and control group revealed a significant (P=0.0003) overrepresentation of combined deletions of both GSTM1 and GSTT1 (double null genotype) in the group of patients with AML/MDS secondary to chemo- and/or radiotherapy of a carcinoma of the breast. In this group, 55% of the patients displayed the double null genotype as compared with 8.8% in the control group. We conclude that patients with carcinoma of the breast and inheritance of a combined gene deletion of GSTM1 and GSTT1 might bear an increased risk to develop a secondary therapy-induced hematologic neoplasia. An insufficient detoxification of cytostatic drugs such as cyclophosphamide is suggested to represent the underlying pathomechanism.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GSTM1HumanHematologic Neoplasms susceptibilityIAGP associated with Breast NeoplasmsRGD 
GSTT1HumanHematologic Neoplasms susceptibilityIAGP associated with Breast NeoplasmsRGD 
Gstm1RatHematologic Neoplasms susceptibilityISOGSTM1 (Homo sapiens)associated with Breast NeoplasmsRGD 
Gstm1MouseHematologic Neoplasms susceptibilityISOGSTM1 (Homo sapiens)associated with Breast NeoplasmsRGD 
Gstt1RatHematologic Neoplasms susceptibilityISOGSTT1 (Homo sapiens)associated with Breast NeoplasmsRGD 
Gstt1MouseHematologic Neoplasms susceptibilityISOGSTT1 (Homo sapiens)associated with Breast NeoplasmsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gstm1  (glutathione S-transferase mu 1)
Gstt1  (glutathione S-transferase theta 1)

Genes (Mus musculus)
Gstm1  (glutathione S-transferase, mu 1)
Gstt1  (glutathione S-transferase, theta 1)

Genes (Homo sapiens)
GSTM1  (glutathione S-transferase mu 1)
GSTT1  (glutathione S-transferase theta 1)


Additional Information