Abstract
This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers.
Highlights
polycyclic aromatic hydrocarbons (PAHs) are mediated by aryl hydrocarbon receptors (AhR), which are ligand- activated transcriptional factors that play an important role in benzo[a]pyrene-induced carcinogenesis (Shimizu et al, 2000)
Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, Cytochrome P450 1A1 (CYP1A1), GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers
The purpose of this study was to determine the distributions of R273G mutation in tumor suppressor p53 gene (TP53) exon 8, AhR, CYP1A1 and GSTM1 genotypes and to see the effects of PAH on these gene variants, on the one hand, and to see the impacts of AhR, CYP1A1 and GSTM1 genotypes on the R273G mutation in TP53 exon 8 in PAH exposed coke oven workers, on the other hand
Summary
PAHs are mediated by aryl hydrocarbon receptors (AhR), which are ligand- activated transcriptional factors that play an important role in benzo[a]pyrene-induced carcinogenesis (Shimizu et al, 2000). AhR translocates into the nucleus to interact with xenobiotic responsive elements after binding with benzo[a]pyrene (B[a]P) This results the up-regulation of phase I and II enzymes, such as cytochrome P450 (CYP450) and glutathione S-transferases (GST), which are involved in the metabolism of PAHs (Jiang et al, 2005). AhR polymorphisms will cause higher binding affinities or more functionally efficient which makes their carriers more sensitive to environment compounds exposure (Maier et al, 1998; Ramadoss et al, 2005; Gu et al, 2012). Kawajiri and his colleagues firstly found one of the polymorphisms in human AhR, G1661A (Arg 554 Lys; rs2066853). This polymorphism has been the most commonly studied in the AhR gene polymorphism since (Kawajiri et al, 1995)
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