Polymorphisms of glutathione S‐transferase mu1 (GSTM1) and theta 1 (GSTT1) genes in chronic myeloid leukaemia

Lourenço, Gustavo Jacob; Ortega, Manoela Marques; Nascimento, Helvia; Teori, Maria T.; Souza, Cármino Antônio de; Costa, Fernando Ferreira; Lima, Carmen Sílvia Passos

doi:10.1111/j.1600-0609.2005.00567.x

Cited by 20 publications

(16 citation statements)

References 8 publications

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“…Only Lemos et al found increased risk of CML for the GSTM1 null genotype, but that study included only 11 cases of CML. Although our study lacked a matched design and contained a modest number of cases and controls, its size and design are similar to those of other studies reported in the literature .…”

Section: Discussionmentioning

confidence: 99%

Variations in glutathione‐S‐transferase genes influence risk of chronic myeloid leukemia

Özten

Sunguroğlu

Bosland

2011

Hematological Oncology

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Glutathione S-transferases (GSTs) are phase II enzymes that detoxify hazardous xenobiotics including carcinogens. Inter-individual variations in GSTM1 and GSTT1 loci have been associated with several types of cancer, including leukemias. In this study, we investigated the possible association between GSTM1 and GSTT1 polymorphisms and susceptibility to chronic myeloid leukemia (CML) in a Turkish population. In a case-control study, 106 CML patients and 190 healthy controls were evaluated for GSTM1 and GSTT1 polymorphisms. GSTM1 null (GSTM1(-)) genotype frequencies in CML cases and controls were 45.3% and 42.6%, respectively. GSTT1 null (GSTT1(-)) genotype frequencies were 44.3% and 18.4%, respectively. The frequency of the GSTT1(-) genotype among CML patients was significantly higher than in controls [odds ratio (OR) 3.53, 95% confidence interval (CI) 2.08-6.00; P < 0.0001]. Individuals with the GSTM1(-) genotype did not have increased risk of CML [OR: 1.11; 95% CI: 0.69-1.80; P = 0.714]. The combined GSTM1(-)/GSTT1(-) genotype was significantly associated with risk of CML compared to the GSTM1(+) /GSTT1(+) genotype which was most frequent in both cases and controls [OR: 9.47; 95% CI: 3.61-24.87]. Similar findings have only been obtained in Turkish and Indian populations but not elsewhere. The GSTM1(+) /GSTT1(-) genotype was associated with a 2.5-fold increased risk compared with the GSTM1(-)/GSTT1(+) genotype, the second most frequent genotype (OR; 2.46; 95% CI: 1.17, 5.20), suggesting a complex interaction between GSTM1 and GSTT1. Our results indicate an association between the GSTT1(-) genotype, either alone or in combination with GSTM1(-) genotype, and risk of CML, suggesting a possible interaction between GSTM1 and GSTT1. These findings, which are possibly restricted to Turkey and India, warrant further research.

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Section: Discussionmentioning

confidence: 99%

Variations in glutathione‐S‐transferase genes influence risk of chronic myeloid leukemia

Özten

Sunguroğlu

Bosland

2011

Hematological Oncology

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“…Moreover, the GSTM1 non-null genotype has already been reported in a higher frequency in CML patients than in controls among Japanese (Hishida et al, 2005). None of the published articles have performed OR or association studies using GSTM1 non-null genotype; they have only analyzed the CML risk for the GSTM1 null genotype or in combination with GSTT1 (Hishida et al, 2005;Lourenço et al, 2005;Mondal et al, 2005;Souza et al, 2008). This may be because it is unbelievable that the presence of an enzyme, which operates in carcinogen detoxification, could increase cancer risk, while its lack could protect against it.…”

Section: Discussionmentioning

confidence: 99%

“…Because these genes may be deleted, resulting in deficiency of GST activities (Hengstler et al, 1998) and in diminished ability to detoxify various carcinogens (Crump et al, 2000), environmental exposure to cytotoxic and genotoxic agents could increase CML risk for individuals carrying GST deletions. Indeed, an increased GSTT1 null genotype frequency has been observed in CML patients (Mondal et al, 2005), and GSTM1 polymorphism has been suggested as important in CML etiology (Lourenço et al, 2005). Given interethnic and intra-ethnic differences in GST allele frequencies (Cotton et al, 2000;Landi, 2000), association studies between GSTM1/T1 polymorphisms with CML risk in different ethnicities may help us to better understand the heterogeneity of the disease and of patients' response to treatment.…”

Section: Introductionmentioning

confidence: 99%

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population

Lordelo¹,

Miranda-Vilela²,

Akimoto³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-G.S. Lordelo et al. 1014©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (2): 1013-1026 (2012) 0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.

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“…The polymorphic form of GSTT1 results in a partial or complete deletion of the gene, which has been found to cause deficiency in enzyme activity ( Hallier et al, 1993). Varied results have been reported on the GSTM1 and GSTT1 null genotype and its association to CML in different ethnic populations ( Weber , 1999;Roy et al, 2001;Mondal et al, 2005;Lourenco et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

Bhat

Bhat²,

Wani³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ± S.D) 42.3 ± 13.4 years) and unrelated non-malignant controls (76 male and 48 females; age (mean ± S.D) 41.5 ± 12.9). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

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Polymorphisms of glutathione S‐transferase mu1 (GSTM1) and theta 1 (GSTT1) genes in chronic myeloid leukaemia

Cited by 20 publications

References 8 publications

Variations in glutathione‐S‐transferase genes influence risk of chronic myeloid leukemia

Variations in glutathione‐S‐transferase genes influence risk of chronic myeloid leukemia

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population

Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

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