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 onthe 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 workerswere recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation inblood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine usingthe high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinaryexcretion 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 smokingsubjects (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/Argfor 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 toPAH related cancers.