Impact of AhR, CYP1A1 and GSTM1 genetic polymorphisms on TP53 R273G mutations in individuals exposed to polycyclic aromatic hydrocarbons.

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.

• Authors: Meili Gao, Yongfei Li, Xiaochang Xue, Jiangang Long, Lan Chen, Walayat Shah, Yu Kong
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 15 Issue 6 Pg. 2699-705 ( 2014) ISSN: 2476-762X [Electronic] Thailand
• PMID: 24761888 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AHR protein, human
• Basic Helix-Loop-Helix Transcription Factors
• Polycyclic Aromatic Hydrocarbons
• Receptors, Aryl Hydrocarbon
• TP53 protein, human
• Tumor Suppressor Protein p53
• Aromatase
• CYP19A1 protein, human
• Glutathione Transferase
• glutathione S-transferase M1

Topics

• Adult
• Aromatase (genetics)
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Case-Control Studies
• Chromatography, High Pressure Liquid
• DNA Damage (genetics)
• Follow-Up Studies
• Genotype
• Glutathione Transferase (genetics)
• Humans
• Male
• Mutation (genetics)
• Occupational Diseases (chemically induced, genetics, urine)
• Occupational Exposure (adverse effects)
• Polycyclic Aromatic Hydrocarbons (adverse effects)
• Polymorphism, Genetic (genetics)
• Prognosis
• Receptors, Aryl Hydrocarbon (genetics)
• Tumor Suppressor Protein p53 (genetics)