The Role of Cyp2e1 Polymorphism in the Activation of Procarcinogen Metabolism of Nasopharyngeal Carcinoma

Farhat, Farhat; Daulay, Elvita Rahmi; Chrestella, Jessy

doi:10.32734/ijnpc.v1i03.2063

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…Meanwhile, the rs3813867 polymorphism of CYP2E1 results from the substitution of guanine with cytosine at the 1259th position, whereas rs6413432 involves a substitution of thymine with adenine at the 7678th position of the gene 38 . These substitutions may lead to altered binding affinity of transcription factors and other regulatory elements, causing changes in the amount of protein product and subsequently the risk of cancer 39 .…”

Section: Discussionmentioning

confidence: 99%

Association between CYP2E1 polymorphisms and colorectal cancer risk: a systematic review and meta-analysis

Sharzehan

Sito

Abdullah

et al. 2022

Sci Rep

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CYP2E1 encodes an enzyme that participates in the activation of several carcinogenic substances. Thus, numerous studies have investigated the association between CYP2E1 polymorphisms and colorectal cancer (CRC) risk, but inconclusive results have been obtained. We performed a meta-analysis to precisely evaluate the relationship of CYP2E1 rs2031920, rs3813867, and rs6413432 polymorphisms with the susceptibility to CRC. Scopus, Web of Science and PubMed databases were searched to identify eligible studies, and the association between the polymorphisms and CRC risk was then quantitatively synthesized using different genetic models. Eighteen studies with 23,598 subjects were selected for inclusion into the analysis. Significant association between rs2031920 and an increased CRC risk was observed in homozygous (OR = 1.496, 95% CI 1.177–1.901, P = 0.001), recessive (OR = 1.467, 95% CI 1.160–1.857, P = 0.001) and allele (OR = 1.162, 95% CI 1.001–1.349, P = 0.048) models. Significant association was not found for rs3813867 and rs6413432 (P > 0.05). In conclusion, our results suggest that rs2031920, but not rs3813867 and rs6413432, is associated with the risk of CRC.

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Section: Discussionmentioning

confidence: 99%

Association between CYP2E1 polymorphisms and colorectal cancer risk: a systematic review and meta-analysis

Sharzehan

Sito

Abdullah

et al. 2022

Sci Rep

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“…Diethylnitrosamine (DEN) is widely used as a carcinogen in animal models to induce hepatocarcinogenesis and its mechanism of action is well-documented (Hadem et al, 2014;Hamza et al, 2021). DEN is a pro-carcinogen and it require metabolic activation by Cytochrome P450 2E1 (CYP2E1) a part of CYP 450 enzyme families (Farhat et al, 2019). The metabolically active compound induce DNA ethyl-adduct leading to hepatocellular cancer (Helms et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Modulation of EphA7 and pEphA7 Protein Expression: Potential Biomarkers for Early Detection of Hepatocellular Carcinoma

Priya

Kma

2022

Asian Pac J Cancer Prev

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Background: Hepatocellular carcinoma (HCC) is one of the leading drivers of cancer-related mortality in the world. As a result, researchers are constantly looking for ways to optimize the screening and diagnosis of the said malignancy. Objective: To establish the mice model of hepatocellular carcinoma with the administration of a suitable dose of diethylnitrosamine (DEN) and examine the utility of EphA7 and pEphA7 as ideal diagnostic markers in HCC. Methods: Swiss Albino (BALB/c) mice of around 10-12 weeks old were exposed to a known hepatocarcinogen-diethylnitrosamine at a dose of 20 mg/kg body weight at weekly intervals for a period of 4, 8, 12, & 16 weeks. Blood was collected from mice of different experimental groups, and age-matched control and serum were separated from whole blood samples. The liver homogenate was prepared after completion of treatment, and the resulting supernatant was used for enzyme assays. A range of liver biomarker enzyme assays such as Gamma-glutamyl transpeptidase (GGT), Acetylcholine esterase (AChE), GPx activity and GSH level, Heme oxygenase-1 (HO-1), GPC3 and alpha-fetoprotein (AFP) level along with the expression of Caspase-3, EphA7 and pEphA7 were evaluated. Results: An elevation in body weight and relative liver weight across the treatment period (4, 8, 12, 16 weeks) was observed in DEN-treated mice. Significant differences in GGT levels between control and DEN treated mice were noted in the present study (P < 0.005). In the 16th week of the treatment period, a significant difference in AchE level was noted between the treated and control group (P < 0.001). However, there was no statistically significant difference in the levels of SGOT and SGPT levels between the control and DEN treated groups (P > 0.001). Lower GSH and GPx levels were demonstrated in the treated mice as compared to control over all the treatment period. Loss of Caspase-3 expression and significant differences in expression of HO-1 activity in treated vs. non-treated group of mice were observed. Significant differences in EphA7 and pEphA7 protein expression levels were noted in the DEN-treated vs. control groups across all the treatment periods (4 weeks: P < 0.05; 8 weeks: P < 0.05; 12 weeks: P < 0.005; 16 weeks: P < 0.05). Conclusion: The present study indicated that EphA7 and phosphoEphA7 over-expression might contribute to the malignancy transition, invasion development, and metastasis of HCC. As a result, along with the known markers such as AFP and others, EphA7 and pEphA7 could be a very putative biomarkers of HCC, particularly at a very early stage of cancer development.

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Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population

Alami,

Khaali,

Jalbout

et al. 2024

Annals of Human Genetics

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BackgroundNasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between CYP2E1 (rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management.MethodsA total of 600 NPC cases and 545 controls frequency‐matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of CYP2A6 and CYP2E1(rs3813867) was performed by polymerase chain reaction restriction (PCR)‐fragment length polymorphism (RFLP) analysis and the GSTM1 (rs1183423000) and GSTT1(rs1601993659) genetic variations were evaluated using the PCR technique.ResultsThe genotype distributions of CYP2E1(rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) genotypes did not differ significantly among NPC cases and controls (p > 0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking.ConclusionIn this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility.

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The Role of Cyp2e1 Polymorphism in the Activation of Procarcinogen Metabolism of Nasopharyngeal Carcinoma

Cited by 3 publications

References 40 publications

Association between CYP2E1 polymorphisms and colorectal cancer risk: a systematic review and meta-analysis

Association between CYP2E1 polymorphisms and colorectal cancer risk: a systematic review and meta-analysis

Modulation of EphA7 and pEphA7 Protein Expression: Potential Biomarkers for Early Detection of Hepatocellular Carcinoma

Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population

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