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Contributions of Aryl Hydrocarbon Receptor Genetic Variants to the Risk of Glioma and PAH-DNA Adducts

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机构: [1]Nanjing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Nanjing 210029, Jiangsu, Peoples R China; [2]Nanjing Med Univ, Sch Publ Hlth, State Key Lab Reprod Med, Inst Toxicol, Nanjing 210029, Jiangsu, Peoples R China; [3]Minist Environm Protect, Key Lab Pesticide Environm Assessment & Pollut Co, Nanjing Inst Environm Sci, Nanjing 210042, Jiangsu, Peoples R China; [4]Capital Med Univ, Tiantan Hosp, Dept Neurosurg, Beijing 100050, Peoples R China; [5]Nanjing Med Univ, Affiliated Hosp 1, Dept Neurosurg, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China
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关键词: aryl hydrocarbon receptor (AHR) polymorphism glioma PAH-DNA adducts

摘要:
The aryl hydrocarbon receptor (AHR) gene is involved in the response to polycyclic aromatic hydrocarbon (PAH) exposure. To investigate the hypothesis that the genetic variants in the AHR gene might be a causal genetic susceptibility to PAH-DNA adduct formation and glioma risk, we conducted a case-control study of 384 glioma cases and 384 cancer-free controls to explore the association between six common single-nucleotide polymorphisms of the AHR gene and glioma risk. Using PAH-DNA adducts as biomarkers, we then evaluated the association between PAH-DNA adduct levels and glioma risk based on a tissue microarray including 11 controls and 77 glioma patients. We further explored the contributions of the glioma risk associated AHR polymorphisms to the levels of PAH-DNA adducts in glioma tissues based on 77 glioma patients. We found that PAH-DNA adduct staining existed in normal brain tissues and grades I-IV gliomas, and the staining intensity was significantly associated with the glioma grade. Two AHR polymorphisms (rs2066853 and rs2158041) demonstrated significant association with glioma risk. Intriguingly, we also found statistically significant associations between these two variants and PAH-DNA adduct levels in glioma tissue. These data suggest the contributions of AHR rs2066853 and rs2158041 to glioma risk and the PAH-DNA adduct levels, which shed new light on gene-environment interactions in the etiology of glioma. Further studies with a larger sample size and ethnically diverse populations are required to elucidate the potential biological mechanism for, as well as the impact of, the susceptibility to glioma due to genetic variants of AHR.

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出版当年[2011]版:
大类 | 2 区 医学
小类 | 2 区 毒理学
最新[2023]版:
大类 | 3 区 医学
小类 | 2 区 毒理学
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出版当年[2010]版:
Q1 TOXICOLOGY
最新[2023]版:
Q2 TOXICOLOGY

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第一作者机构: [1]Nanjing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Nanjing 210029, Jiangsu, Peoples R China; [2]Nanjing Med Univ, Sch Publ Hlth, State Key Lab Reprod Med, Inst Toxicol, Nanjing 210029, Jiangsu, Peoples R China;
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通讯机构: [1]Nanjing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Nanjing 210029, Jiangsu, Peoples R China; [5]Nanjing Med Univ, Affiliated Hosp 1, Dept Neurosurg, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China
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