Genetic polymorphisms of NQO1, CYP1A1 and TPMT and susceptibility to acute lymphoblastic leukemia in a Tunisian population

Ouerhani, Slah; Cherif, Nouha; Bahri, Ikbel; Safra, Ines; Menif, Samia; Abbès, Salem

doi:10.1007/s11033-012-2174-y

Cited by 20 publications

(12 citation statements)

References 42 publications

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“…Among the articles, 18 and 18 were about the associations of the NQO1 C609T polymorphism with the risks of AML and ALL, respectively, two were about the association between the NQO1 C465T polymorphism and the AML risk, and three were about the association between the NQO1 C465T polymorphism and the ALL risk. Among these studies, 11 focused on Caucasians,1,3,12–20 10 on Asians,2,9,10,21–27 four on mixed populations,5,28–30 two on Africans,31,32 and one on Javanese 33. In terms of the genotype distribution of controls, 20 of the studies about the association between the NQO1 C609T polymorphism and the AL risk conformed with HWE,1,3,5,9,12,14–20,22–24,28,30–33 while seven did not,2,10,21,25–27,29 and the HWE test could not be applied to one study13 because of insufficient data.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the influence analysis of single study showed that the total pooled result was greatly affected by the 15 studies (Figure 2B). 2,3,9,10,12,13,15,16,19,21,25,28–31 Excluding any of these studies resulted in the statistically significant loss of pooled OR values. Meanwhile, the sensitivity analysis revealed that deleting two studies of low quality,2,13 five studies that did not conform to HWE,2,10,21,25,29 or one study for which the HWE test was not applied did not change the pooled ORs,13 showing that these factors did not affect the stability of the pooled results.…”

Section: Resultsmentioning

confidence: 99%

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Associations of NQO1 C609T and NQO1 C465T polymorphisms with acute leukemia risk: a PRISMA-compliant meta-analysis

He¹,

Zhai²,

Liu³

et al. 2017

OTT

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ObjectiveThe NAD(P)H:quinone oxidoreductase (NQO1) C609T and C465T polymorphisms have been widely thought to be associated with the risk of acute leukemia (AL) in recent years, but the correlations are still unclear. A meta-analysis is generally acknowledged as one of the best methods for secondary research, and so it was applied in this study with the aim of elucidating how the NQO1 C609T and C465T polymorphisms are related to the risk of AL.MethodsRelevant studies were searched in the PubMed, EMBASE, CNKI, and Wanfang databases, and the obtained data were analyzed using Stata (version 12.1). The allele-contrast model was applied, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationship strengths. Meta-regression was used to identify sources of heterogeneity, and subgroup analyses were conducted. Publication bias was analyzed using funnel plots, with the trim-and-fill method used to analyze the effect of publication bias on pooled results. In addition, sensitivity analysis, the fail-safe number method, and cumulative analysis by publication year were performed to measure the stability of the obtained results.ResultsThis meta-analysis included 28 relevant studies involving 5,953 patients and 8,667 controls. Overall, the C609T polymorphism was associated with the risk of acute lymphoblastic leukemia (ALL; OR =1.18, 95% CI =1.00–1.39, P=0.05). Meanwhile, race was found to be a potential source of heterogeneity for the relationship between the C609T polymorphism and acute myeloid leukemia (AML) risk, and the subgroup analysis identified the C609T polymorphism as a risk factor for AML in Asians (OR =1.34, 95% CI =1.03–1.74, P=0.03). The number of studies about C465T polymorphism was too small to pool the data.ConclusionThere are increased risks of ALL in all subjects and of AML in Asians for carriers of the NQO1 C609T polymorphism. Further studies are needed to verify the associations of the C465T polymorphism with the risk of AL.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Associations of NQO1 C609T and NQO1 C465T polymorphisms with acute leukemia risk: a PRISMA-compliant meta-analysis

He¹,

Zhai²,

Liu³

et al. 2017

OTT

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“…This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase which reduces quinones to hydroquinones. Lower NQO1 activity caused by gene mutations has been associated with tardive dyskinesia,48 an increased pulmonary susceptibility to ozone,49 and susceptibility to various forms of cancer 50,51. In addition, NQO1 binds and protects the tumor suppressor p53 against proteasomal degradation; thus, it has even broader cytoprotective roles, beyond its enzymatic functions 52…”

Section: Review Of Genes and Results For Degenerative And Immunologicmentioning

confidence: 99%

The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

Gao¹,

Doan²,

Hybertson³

2014

CPAA

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Nuclear factor (erythroid-derived 2)-like 2 (Nrf2; encoded in humans by the NFE2L2 gene) is a transcription factor that regulates the gene expression of a wide variety of cytoprotective phase II detoxification and antioxidant enzymes through a promoter sequence known as the antioxidant-responsive element (ARE). The ARE is a promoter element found in many cytoprotective genes; therefore, Nrf2 plays a pivotal role in the ARE-driven cellular defense system against environmental stresses. Agents that target the ARE/Nrf2 pathway have been tested in a wide variety of disorders, with at least one new Nrf2-activating drug now approved by the US Food and Drug Administration. Examination of in vitro and in vivo experimental results, and taking into account recent human clinical trial results, has led to an opinion that Nrf2-activating strategies – which can include drugs, foods, dietary supplements, and exercise – are likely best targeted at disease prevention, disease recurrence prevention, or slowing of disease progression in early stage illnesses; they may also be useful as an interventional strategy. However, this rubric may be viewed even more conservatively in the pathophysiology of cancer. The activation of the Nrf2 pathway has been widely accepted as offering chemoprevention benefit, but it may be unhelpful or even harmful in the setting of established cancers. For example, Nrf2 activation might interfere with chemotherapies or radiotherapies or otherwise give tumor cells additional growth and survival advantages, unless they already possess mutations that fully activate their Nrf2 pathway constitutively. With all this in mind, the ARE/Nrf2 pathway remains of great interest as a possible target for the pharmacological control of degenerative and immunological diseases, both by activation and by inhibition, and its regulation remains a promising biological target for the development of new therapies.

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“…A recent focus of current research has been the identification of polymorphisms in NQO1, which have been demonstrated as an increased risk of some tumors. Ouerhani et al reported that the NQO1C609T genotype was overrepresented in acute lymphoblastic leukemia patients and was associated with an aggravating effect compared to the reference group with NQO1 C609C genotype [24]. Jamieson et al reported the NQO1 SNP (rs1800566) was associated with a poorer outcome and a lower likelihood of having a treatment delay [25].…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of high NQO1 expression in breast cancers

Yang

Zhang

et al. 2014

J Exp Clin Cancer Res

150

126

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BackgroundNAD (P) H: quinone oxidoreductase 1 (NQO1) is a xenobiotic metabolizing enzyme that detoxifies chemical stressors and antioxidants, providing cytoprotection in normal tissues. However, high-level expression of NQO1 has been correlated with numerous human malignancies, suggesting a role in carcinogenesis and tumor progression. This study aimed to explore the clinicopathological significance of NQO1 and as a prognostic determinant in breast cancer.MethodsA total of 176 breast cancer patients with strict follow-up, 45 ductal carcinoma in situ (DCIS), 22 hyperplasia and 52 adjacent non-tumor breast tissues were selected for immunohistochemical staining of NQO1 protein. Immunofluorescence staining was also performed to detect the subcellular localization of NQO1 protein in MCF-7 breast cancer cells. Eight fresh breast cancers paired with adjacent non-tumor tissues were quantified using real time RT-PCR (qRT-PCR) and western blot. The correlations between NQO1 overexpression and the clinical features of breast cancer were evaluated using chi-square test and Fisher’s exact tests. The survival rate was calculated using the Kaplan–Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazards models.ResultsNQO1 protein showed a mainly cytoplasmic staining pattern in breast cancer. The strongly positive rate of NQO1 protein was 61.9% (109/176) in breast cancer, and was significantly higher than in DCIS (31.1%, 14/45), hyperplasia tissues (13.6%, 3/22) and adjacent non-tumor tissues (13.5%, 7/52). High-level expression of NQO1 protein was correlated with late clinical stage, poor differentiation, lymph node metastasis, Her2 expression and disease-free and 10-year overall survival rates in breast cancer. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer.ConclusionsHigh-level expression of NQO1 appears to be associated with breast cancer progression, and may be a potential biomarker for poor prognostic evaluation of breast cancers.

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Genetic polymorphisms of NQO1, CYP1A1 and TPMT and susceptibility to acute lymphoblastic leukemia in a Tunisian population

Cited by 20 publications

References 42 publications

Associations of NQO1 C609T and NQO1 C465T polymorphisms with acute leukemia risk: a PRISMA-compliant meta-analysis

Associations of NQO1 C609T and NQO1 C465T polymorphisms with acute leukemia risk: a PRISMA-compliant meta-analysis

The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

Clinical implications of high NQO1 expression in breast cancers

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