RGD Reference Report - Pharmacogenetic influence of GST polymorphisms on anthracycline-based chemotherapy responses and toxicity in breast cancer patients: a multi-analytical approach. - Rat Genome Database

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Pharmacogenetic influence of GST polymorphisms on anthracycline-based chemotherapy responses and toxicity in breast cancer patients: a multi-analytical approach.

Authors: Tulsyan, S  Chaturvedi, P  Agarwal, G  Lal, P  Agrawal, S  Mittal, RD  Mittal, B 
Citation: Tulsyan S, etal., Mol Diagn Ther. 2013 Dec;17(6):371-9. doi: 10.1007/s40291-013-0045-4.
RGD ID: 10755330
Pubmed: PMID:23812950   (View Abstract at PubMed)
DOI: DOI:10.1007/s40291-013-0045-4   (Journal Full-text)

BACKGROUND AND OBJECTIVE: Chemotherapeutic drug treatment outcomes are genetically determined. Polymorphisms in genes encoding phase II drug metabolizing enzyme glutathione-S-transferase (GST) can possibly predict treatment outcomes, and can be of prognostic significance in breast cancer patients. The aim of this study was to determine the role of genetic variations in GST in predicting response to, and toxicity of, anthracycline-based chemotherapy in breast cancer patients. METHOD: Two hundred and seven patients treated with anthracycline-based chemotherapy were genotyped for GSTM1 and GSTT1 deletion polymorphisms, and GSTP1 Ile105Val (rs1695), by polymerase chain reaction (PCR)/ PCR-restriction fragment length polymorphism (RFLP). Genetic variations were correlated with tumor response to neo-adjuvant chemotherapy (NACT) in 100 patients, and with chemo-toxicity in 207 who received adjuvant chemotherapy or NACT, using Chi-square and logistic regression. Higher order gene-gene interactions with treatment outcomes were characterized by multifactor dimensionality reduction (MDR) analysis. RESULTS: In single-locus analysis, Ile/Val and Ile/Val+Val/Val genotypes of the GSTP1 Ile105Val (rs1695) polymorphism reached statistical significance with grade 2-4 anemia (P=0.019, P=0.027). On performing gene-gene interaction analysis, GSTM1 null-GSTP1 Ile/Val was significantly associated with response to NACT (P=0.032). On evaluating higher order gene-gene interaction models by MDR analysis, GSTM1 and GSTP1 Ile105Val; GSTM1 and GSTT1; and GSTT1 and GSTP1 Ile105Val showed significant association with treatment response, grade 2-4 anemia, and dose delay/reduction due to neutropenia (P=0.046, P=0.027, P=0.026), respectively. CONCLUSION: Multi-analytical strategies may serve as a better tool for characterization of pharmacogenetic-based breast cancer treatment outcomes.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GSTM1Humanbreast cancer treatmentIAGP  RGD 
GSTP1Humanbreast cancer treatmentIAGP DNA:SNP:cds:p.I105V (rs1695) (human)RGD 
Gstm1Ratbreast cancer treatmentISOGSTM1 (Homo sapiens) RGD 
Gstm1Mousebreast cancer treatmentISOGSTM1 (Homo sapiens) RGD 
Gstp1Ratbreast cancer treatmentISOGSTP1 (Homo sapiens)DNA:SNP:cds:p.I105V (rs1695) (human)RGD 
Gstp1Mousebreast cancer treatmentISOGSTP1 (Homo sapiens)DNA:SNP:cds:p.I105V (rs1695) (human)RGD 
GSTM1HumanDrug-induced Anemia susceptibilityIAGP associated with breast cancerRGD 
GSTT1HumanDrug-induced Anemia susceptibilityIAGP associated with breast cancerRGD 
Gstm1MouseDrug-induced Anemia susceptibilityISOGSTM1 (Homo sapiens)associated with breast cancerRGD 
Gstm1RatDrug-induced Anemia susceptibilityISOGSTM1 (Homo sapiens)associated with breast cancerRGD 
Gstt1RatDrug-induced Anemia susceptibilityISOGSTT1 (Homo sapiens)associated with breast cancerRGD 
Gstt1MouseDrug-induced Anemia susceptibilityISOGSTT1 (Homo sapiens)associated with breast cancerRGD 
GSTP1HumanDrug-induced Neutropenia susceptibilityIAGP DNA:SNP:cds:p.I105V (rs1695) (human)RGD 
GSTT1HumanDrug-induced Neutropenia susceptibilityIAGP associated with breast cancerRGD 
Gstp1MouseDrug-induced Neutropenia susceptibilityISOGSTP1 (Homo sapiens)DNA:SNP:cds:p.I105V (rs1695) (human)RGD 
Gstp1RatDrug-induced Neutropenia susceptibilityISOGSTP1 (Homo sapiens)DNA:SNP:cds:p.I105V (rs1695) (human)RGD 
Gstt1RatDrug-induced Neutropenia susceptibilityISOGSTT1 (Homo sapiens)associated with breast cancerRGD 
Gstt1MouseDrug-induced Neutropenia susceptibilityISOGSTT1 (Homo sapiens)associated with breast cancerRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gstm1  (glutathione S-transferase mu 1)
Gstp1  (glutathione S-transferase pi 1)
Gstt1  (glutathione S-transferase theta 1)

Genes (Mus musculus)
Gstm1  (glutathione S-transferase, mu 1)
Gstp1  (glutathione S-transferase, pi 1)
Gstt1  (glutathione S-transferase, theta 1)

Genes (Homo sapiens)
GSTM1  (glutathione S-transferase mu 1)
GSTP1  (glutathione S-transferase pi 1)
GSTT1  (glutathione S-transferase theta 1)


Additional Information