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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30901534, 81172694, 30901210]; Jiangsu Province's Natural Science FoundationNatural Science Foundation of Jiangsu Province [BK2009444]; Grant for the 135 Key Medical Project of Jiangsu Province [XK201117]; National High Technology Research and Development Program 863National High Technology Research and Development Program of China [2012AA02A508]; Jiangsu Province's Medical Major Talent program [RC2011051]
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;
通讯作者:
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
推荐引用方式(GB/T 7714):
Gu Aihua,Ji Guixiang,Jiang Tao,et al.Contributions of Aryl Hydrocarbon Receptor Genetic Variants to the Risk of Glioma and PAH-DNA Adducts[J].TOXICOLOGICAL SCIENCES.2012,128(2):357-364.doi:10.1093/toxsci/kfs158.
APA:
Gu, Aihua,Ji, Guixiang,Jiang, Tao,Lu, Ailin,You, Yongping...&Zhao, Peng.(2012).Contributions of Aryl Hydrocarbon Receptor Genetic Variants to the Risk of Glioma and PAH-DNA Adducts.TOXICOLOGICAL SCIENCES,128,(2)
MLA:
Gu, Aihua,et al."Contributions of Aryl Hydrocarbon Receptor Genetic Variants to the Risk of Glioma and PAH-DNA Adducts".TOXICOLOGICAL SCIENCES 128..2(2012):357-364