Impact of AhR, CYP1A1 and GSTM1 genetic polymorphisms on TP53 R273G mutations in individuals exposed to polycyclic aromatic hydrocarbons.
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.
Institute of Mitochondrial Biology and Medicine, Department of Biological Science and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China E-mail : gaomeili@mail.xjtu.edu.cn.
Meili
M
Gao
Yongfei
Y
Li
Xiaochang
X
Xue
Jiangang
J
Long
Lan
L
Chen
Walayat
W
Shah
Yu
Y
Kong
D000328:Adult; D001141:Aromatase / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000235:genetics; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009784:Occupational Diseases / Q000139:chemically induced / Q000235:genetics / Q000652:urine*; D016273:Occupational Exposure / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D001141:Aromatase; D051792:Basic Helix-Loop-Helix Proteins; D005982:Glutathione Transferase; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D016159:Tumor Suppressor Protein p53; C111235:AHR protein, human; C495901:TP53 protein, human; C561410:CYP19A1 protein, human