Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors.
Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors.
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DOI：
10.1158/1055-9965.epi-09-0197
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
Rajaraman P
中科院分区：
文献类型：
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作者：
Bhatti P;Stewart PA;Hutchinson A;Rothman N;Linet MS;Inskip PD;Rajaraman P
有一些证据表明，氧化应激在铅诱导的毒性中起作用。考虑到高氧代谢率，处理氧化应激的机制可能与大脑特别相关。通过一项基于医院的病例对照研究，我们通过检测与氧化应激相关功能基因的单核苷酸多态性（snp）对职业性铅暴露与脑肿瘤之间关系的影响改变，研究了氧化应激在铅潜在致癌性中的作用。该研究包括362例胶质瘤患者（其中176例为胶质母细胞瘤），134例脑膜瘤患者和494例对照。通过专家对每个参与者的详细工作历史数据的审查来估计铅暴露。我们使用似然比检验评估了142个snp的效应修饰，比较了嵌套的无条件逻辑回归模型，这些模型包含和不包含累积铅暴露和基因型的交叉产品项。当分析仅限于GBM病例时，经多重比较调整后，发现RAC2 rs2239774和两个高度相关的GPX1多态性（rs1050450和rs18006688）显著改变了与铅暴露的关联（p≤0.05）。此外，同样的GPX1多态性和XDH rs7574920被发现显著改变了累积铅暴露与脑膜瘤之间的关系。虽然这项研究的结果提供了一些证据，表明铅可能通过与氧化损伤相关的机制导致GBM和脑膜瘤，但这一结果必须在其他人群中得到证实。
There is some evidence that oxidative stress plays a role in lead-induced toxicity. Mechanisms for dealing with oxidative stress may be of particular relevance in the brain, given the high rate of oxygen metabolism. Using a hospital-based case-control study, we investigated the role of oxidative stress in the potential carcinogenicity of lead through examination of effect modification of the association between occupational lead exposure and brain tumors by single nucleotide polymorphisms (SNPs) in genes with functions related to oxidative stress. The study included 362 patients with glioma [176 of which had glioblastoma (GBM)], 134 patients with meningioma and 494 controls. Lead exposure was estimated by expert review of detailed job history data for each participant. We evaluated effect modification with 142 SNPs using likelihood ratio tests that compared nested unconditional logistic regression models that did and did not include a cross-product term for cumulative lead exposure and genotype. When the analyses were restricted to cases with GBM, RAC2 rs2239774 and two highly correlated GPX1 polymorphisms (rs1050450 and rs18006688) were found to significantly modify the association with lead exposure (p ≤ 0.05) after adjustment for multiple comparisons. Furthermore, the same GPX1 polymorphisms and XDH rs7574920 were found to significantly modify the association between cumulative lead exposure and meningioma. While the results of this study provide some evidence that lead may cause GBM and meningioma through mechanisms related to oxidative damage, the results must be confirmed in other populations.