Glutathione S transferase (GSTP 1, GSTM 1, and GSTT 1) gene polymorphisms in Egyptian patients with acute myeloid leukemia

BACKGROUND: The super family of glutathione S-transferases (GSTs) is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some...

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Bibliographic Details
Published in:Indian journal of cancer 2015-10, Vol.52 (4), p.490-495
Main Authors: Nasr, Aml, Sami, Rania, Ibrahim, Noha, Darwish, Dalia
Format: Article
Language:English
Subjects:
Acute myelocytic leukemia
Age
Cancer
Cancer therapies
Chemotherapy
Deoxyribonucleic acid
Development and progression
DNA
Egyptians
Enzymes
Family medical history
Gene expression
Genes
Genetic aspects
Genetic polymorphisms
Genotype & phenotype
Glutathione transferase
Health aspects
Laboratories
Leukemia
Medical prognosis
Polymerase chain reaction
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Summary:BACKGROUND: The super family of glutathione S-transferases (GSTs) is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the body's ability to detoxify a range of potential leukemogens encountered in the environment. AIM OF WORK: To address how differences in the human GST isoenzyme expression patterns influence cancer susceptibility, prognosis, and treatment. PATIENTS AND METHODS: A total of 50 patients with acute myeloid leukemia (AML), as well as 50 age and sex matched apparently healthy volunteers were genotyped for GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and conventional polymerase chain reaction (PCR), respectively. RESULTS: For GSTP1 313 A → G (GSTP1 Ile105Val) polymorphism, It was found that the wild genotype (AA) was significantly higher among control subjects (P value = 0.0277), while the frequency of heteromutant genotype (AG) and mutant G allele (AG + GG) was significantly higher among patients (P value = 0.0402, P value = 0.0277, respectively). For GSTM1 and GSTT1gene, we found statistically significantly higher frequency among patients regarding homozygous gene deletion (P value = 0.0005). CONCLUSION: We demonstrated that GSTM1 null or GSTT1 null genotypes may be considered independent risk factors for AML with no impact on prognosis and GSTP1 * 105 genotype is a prognostic factor, adding independent information to the routine laboratory parameters and cytogenetic and molecular alterations of the tumor cells.
ISSN:0019-509X
1998-4774
DOI:10.4103/0019-509X.178408