Impact of AhR, CYP1A1 and GSTM1 Genetic Polymorphisms on TP53 R273G Mutations in Individuals Exposed to Polycyclic Aromatic Hydrocarbons

Gao, Meili; Li, Yongfei; Xue, Xiaochang; Jiang, Long; Chen, Lan; Shah, Walayat; Kong, Yu

doi:10.7314/apjcp.2014.15.6.2699

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…Intriguingly, AhR is involved in inducing the transcription of several cytochrome P450 enzymes such as CYP1A1, which is critical in metabolizing and bioactivating environmental compounds to highly carcinogenic metabolites [9]. One previous study found that induced CYP1A1 activity was higher in the variant allele A carriers of AhR rs2066853(G>A) polymorphism than those with GG genotype in a Caucasian population [33]. Therefore, some polymorphisms of AhR gene have been suggested as potential causal variants conferring susceptibility to cancer.…”

Section: Discussionmentioning

confidence: 99%

Lack of association between multiple polymorphisms in aryl hydrocarbon receptor (AhR) gene and cancer susceptibility

Luo

Wang

et al. 2020

Environ Health Prev Med

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Background The aryl hydrocarbon receptor (AhR) is commonly known as an environmental sensor. Polymorphisms in AhR gene have been implicated in susceptibility to cancer. However, the results were controversial. This study was conducted to quantitatively summarize the association between AhR polymorphisms and cancer risk by meta-analysis. Methods Relevant reports were searched in four databases (Embase, PubMed, Wanfang, and China National Knowledge Infrastructure). We used pooled odds ratio (OR) and 95% confidence interval (95% CI) to evaluate the strength of the association in both standard and cumulative meta-analysis. Subgroup and sensitivity analysis was also performed, and between-study heterogeneity and publication bias were checked. Results A total of seventeen studies referring to three AhR polymorphisms (rs2066853, rs7796976, and rs2074113) were identified, and 9557 cases and 10038 controls were included. There was no statistically significant association of AhR rs2066853 polymorphism with cancer risk in the overall population, and the negative results were repeated in subgroup analysis by the ethnicity and cancer type. Concerning AhR rs7796976 or rs2074113 polymorphism, no significant correlation was detected. Moreover, these non-significant findings were stable in sensitivity analysis, and the cumulative meta-analysis indicated a trend of no significant link between this three AhR polymorphisms and cancer risk as more data accumulated over time. Conclusion This meta-analysis provides evidence that the rs2066853, rs7796976, or rs2074113 polymorphism in AhR gene is not a susceptible predictor of cancer. Further clinical and functional investigation between AhR polymorphisms and cancer susceptibility are needed.

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Section: Discussionmentioning

confidence: 99%

Lack of association between multiple polymorphisms in aryl hydrocarbon receptor (AhR) gene and cancer susceptibility

Luo

Wang

et al. 2020

Environ Health Prev Med

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“…CYP family proteins serve a role in the oxidative metabolism of endogenous and exogenous molecules, which maintains cardiovascular hemostasis ( 34 ). CYP1A1 is highly expressed in vascular endothelial cells, and there are interactions between PAHs and CYP1A1 ( 35 ). The present results indicated that the expression levels of Hcy and CYP1A1 of Hhcy rats were increased, while Hcy level and CYP1A1 in EA group were decreased, suggesting that there may be some interaction between Hcy and CYP1A1, and EA could reduce the level of them.…”

Section: Discussionmentioning

confidence: 99%

Echinocystic acid ameliorates hyperhomocysteinemia‑induced vascular endothelial cell injury through regulating NF‑κB and CYP1A1

et al. 2017

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The present study investigated the role of echinocystic acid (EA) on the expression of nuclear factor (NF)-κB and cytochrome P450 1A1 (CYP1A1), and aortic morphology, in a rat model of hyperhomocysteinemia (Hhcy). A total of 50 Sprague Dawley rats were randomly divided into five groups as follows: Normal control (NC), model control (MC), vitamin control (VC; folic acid 1 mg/kg + vitamin B2 2 mg/kg + vitamin B12 10u g/kg), EA1 (20 mg/kg EA) and EA2 (40 mg/kg EA). Plasma homocysteine (Hcy) levels were determined via high performance liquid chromatography, and the morphology of the aorta was investigated using hematoxylin and eosin staining. Furthermore, aortic mRNA and protein levels of NF-κB and CYP1A1 were measured using reverse transcription-quantitative polymerase chain reaction analysis and western blotting, respectively. Plasma Hcy levels, and aortic mRNA and protein levels of NF-κB and CYP1A1, were significantly lower in the EA-treated group compared with the MC group (all P<0.05). However, the aortic morphology remained normal, including the endothelial cells of the inner layer, and smooth muscle cells of the media layer and adventitia. In conclusion, the results of the present study indicate that EA has a protective role on vascular endothelial cells in Hhcy through decreasing plasma Hcy, and thus NF-κB and CYP1A1 expression.

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“…7 GSTM1 gene polymorphism can change the ability of the enzymes' activation or deactivation of the heterologous substrate, which can affect individual susceptibility to lung cancer after exposure. [8][9][10][11] Previous studies somehow identified the functional role of CYP2E1 or GSTM1 polymorphism and lung cancer risk; several studies also showed the synergistic interaction between gene polymorphisms and environmental cancerogens, 12 and gene-gene interaction among metabolic enzyme genes, 13,14 but interactions between CYP2E1 and GSTM1 polymorphism, these polymorphisms and environmental factors have seldom been reported, 15 and the results of these studies are not consistent. Besides, lung cancer ranks the first both in incidence and mortality rates of cancer in Zhejiang Province in recent years.…”

Section: C-t Replacement In 5′ Regulatory Region Studies Show That Tmentioning

confidence: 99%

CYP2E1 and GSTM1 gene polymorphisms, environmental factors, and the susceptibility to lung cancer

Wang

Zhang

et al. 2018

Clinical Laboratory Analysis

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Impact of AhR, CYP1A1 and GSTM1 Genetic Polymorphisms on TP53 R273G Mutations in Individuals Exposed to Polycyclic Aromatic Hydrocarbons

Cited by 11 publications

References 42 publications

Lack of association between multiple polymorphisms in aryl hydrocarbon receptor (AhR) gene and cancer susceptibility

Lack of association between multiple polymorphisms in aryl hydrocarbon receptor (AhR) gene and cancer susceptibility

Echinocystic acid ameliorates hyperhomocysteinemia‑induced vascular endothelial cell injury through regulating NF‑κB and CYP1A1

CYP2E1 and GSTM1 gene polymorphisms, environmental factors, and the susceptibility to lung cancer

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