Polymorphisms in the Human Cytochrome P450 and Arylamine<i>N</i>-Acetyltransferase: Susceptibility to Head and Neck Cancers

Khlifi, Rim; Messaoud, Olfa; Rebai, Ahmed; Hamza-Chaffai, Amel

doi:10.1155/2013/582768

Cited by 34 publications

(37 citation statements)

References 168 publications

(262 reference statements)

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“…Thus, 55 publications were eligible. Then, 2 review articles, [ 19 20 ] 3 papers [ 21–23 ] on precancerous lesions, and 1 study [24] on other polymorphic sites of CYP2E1 rather than RsaI/PstI were discarded. Next, 2 studies [ 25 26 ] lacking of controls and 4 studies [ 27–30 ] providing insufficient data were also eliminated.…”

Section: Resultsmentioning

confidence: 99%

Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?

et al. 2016

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Background:Previous reports showed that CYP2E1 RsaI/PstI polymorphism may be a risk factor for cancers. Published meta-analyses in 2010 and 2011, respectively, on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to head and neck carcinoma (HNC) have generated inconsistent results. Thus, this study aimed to conduct an updated meta-analysis involving published studies up to Nov 2015 to get a more confidential result.Methods:Eligible studies up to Nov 2015 were retrieved and screened. Data were extracted and a quantitative meta-analysis was conducted. Subgroup analyses on ethnicity, source of controls, sample size, genotyping method, smoking status, and drinking status were also performed.Results:Forty-one publications including a total of 43 case-control studies were selected for analysis. The overall data under a homozygote comparison model indicated a significant association of CYP2E1 RsaI/PstI polymorphisms with HNC risk (c2c2 vs c1c1: odds ratio [OR] = 1.97; 95% confidence interval [CI] = 1.53–2.53). Similar results were observed in the Asian subgroup (c2c2 vs c1c1: OR = 1.98; 95%CI = 1.51–2.60; c2 vs c1: OR = 1.20; 95%CI = 1.03–1.39) and mixed population (c2 vs c1: OR = 1.41; 95%CI = 1.06–1.86) when the data were stratified by ethnicities. Interestingly, increased cancer risk only was shown among never-smokers (c2c2+c1c2 vs c1c1: OR = 1.44; 95%CI = 1.05–1.98) but not ever-smokers.Conclusion:CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to HNC, particularly among Asians, mixed population, and never-smokers. Future large and well-designed studies are needed to verify this conclusion.

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Section: Resultsmentioning

confidence: 99%

Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?

et al. 2016

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“…For example, when acute myocardial infarction patients were treated with metoprolol (a substrate for CYP2D6) and co-treated with paroxetine (an inhibitor of CYP2D6), paroxetine inhibited the metabolism of metoprolol and increased its concentration maximum (Cmax), resulting in enhanced therapeutic effects and/or adverse effects, such as severe dizziness, fainting and heart failure [34]. In anti-cancer therapy, many studies have demonstrated that altered expression of DMEs can influence the sensitivity and toxicity of drugs in target cells, and the expression of DMEs plays a pivotal role in chemotherapy sensitivity, resistance, and/or carcinogenesis [35,36]. The enzyme activity of CYP2D6 significantly impacts the anti-estrogen effect of tamoxifen in cancer therapy, because it is the most important CYP in the conversion of tamoxifen to 4-OH tamoxifen [37].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA hsa-miR-370-3p suppresses the expression and induction of CYP2D6 by facilitating mRNA degradation

Zeng

Chen

Wang

et al. 2017

Biochemical Pharmacology

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Cytochrome P450 2D6 (CYP2D6) participates in the metabolism of approximately 20–25% of prescribed drugs. Genetic polymorphisms influence the expression and/or activity of CYP2D6, and inter-individual differences in drug activation and elimination caused by CYP2D6 genetic variants were reported. However, little is known about the potential modulation of CYP2D6 expression by microRNAs (miRNAs). In the current study, by using in silico prediction of the stabilities of miRNA/mRNA complexes, we screened 38 miRNA candidates that may interact with the transcript of CYP2D6. An inverse correlation between the expression of miRNA hsa-miR-370-3p and the expression of CYP2D6 was observed in human liver tissue samples. Electrophoretic mobility shift assays confirmed that hsa-miR-370-3p was able to directly bind to its cognate target within the coding region of the CYP2D6 transcript. The transfection of hsa-miR-370-3p mimics into the HepG2CYP2D6 cell line, a genetically modified cell line that overexpresses exogenous CYP2D6, was able to suppress the expression of CYP2D6 significantly at both mRNA and protein levels. The transfection of hsa-miR-370-3p mimics was also able to inhibit endogenous mRNA expression and/or protein production of CYP2D6 in HepaRG cells. Furthermore, in HepaRG, HepG2, and Huh7 cells, dexamethasone-induced expression of CYP2D6 was inhibited by hsa-miR-370-3p mimics. To investigate whether the miRNA mediated suppression is caused by inhibiting protein translation or promoting mRNA degradation, an actinomycin D assay was used to measure the stability of CYP2D6 transcripts. The results indicated that hsa-miR-370-3p mimics facilitated significantly the degradation of CYP2D6 mRNA. In addition, proteomics analyses of proteins isolated from the miRNA/mRNA/protein complex suggested that a group of multifunctional proteins facilitated the interaction between hsa-miR-370-3p and CYP2D6, thereby promoting mRNA degradation.

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“…Once activated, AhR migrates to the nucleus to regulate the expression of genes, such as CYP1A1, which is a member of the cytochrome P450 superfamily of enzymes . CYP1A1 has an essential role in the metabolism of drugs and chemicals, and polymorphisms in this gene have been associated with different tumors …”

Section: Immunomodulatory Features Of Ido Activitymentioning

confidence: 99%

Contribution of IDO to human respiratory syncytial virus infection

Benavente

Soto

Pizarro-Ortega

et al. 2019

Journal of Leukocyte Biology

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IDO is an enzyme that participates in the degradation of tryptophan (Trp), which is an essential amino acid necessary for vital cellular processes. The degradation of Trp and the metabolites generated by the enzymatic activity of IDO can have immunomodulating effects, notably over T cells, which are particularly sensitive to the absence of Trp and leads to the inhibition of T cell activation, cell death, and the suppression of T cell effector functions. Noteworthy, T cells participate in the cellular immune response against the human respiratory syncytial virus (hRSV) and are essential for viral clearance, as well as the total recovery of the host. Furthermore, inadequate or non-optimal polarization of T cells is often seen during the acute phase of the disease caused by this pathogen. Here, we discuss the capacity of hRSV to exploit the immunosuppressive features of IDO to reduce T cell function, thus acquiring relevant aspects during the biology of the virus.Additionally, we review studies on the influence of IDO over T cell activation and its relationship with hRSV infection. K E Y W O R D Sindoleamine-2,3-dioxygenase, tryptophan (Trp), hRSV, T cells J Leukoc Biol. 2019;106:933-942.

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Polymorphisms in the Human Cytochrome P450 and ArylamineN-Acetyltransferase: Susceptibility to Head and Neck Cancers

Cited by 34 publications

References 168 publications

Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?

Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?

MicroRNA hsa-miR-370-3p suppresses the expression and induction of CYP2D6 by facilitating mRNA degradation

Contribution of IDO to human respiratory syncytial virus infection

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