Lead And Other Neurotoxins As Risk Factors For ALS

目的：研究ALS与铅暴露于其他神经毒素(如汞、溶剂和农药)的潜在相关性。生活方式因素如吸烟和饮食基因多态性影响神经功能或铅代谢成就：我们主要关注ALS与铅暴露的关系。铅水平升高与骨骼和血液的肌萎缩侧索硬化症相关。血铅每增加一单位，患病风险增加1.7倍，膝盖骨铅每增加一单位，患病风险增加5.3倍，胫骨铅每增加一单位，患病风险增加4.2倍。然而，病例和对照组的铅水平都在正常范围内。这些结果可能表明，即使铅水平略有上升，长期暴露也会增加患ALS的风险。我们还发现，ALS的风险与自我报告的职业铅暴露有关。在那些曾经从事过与铅接触有关的工作的参与者中，患肌萎缩侧索硬化症的风险要高出1.9倍，而且一生中接触铅的日子都存在剂量反应。在最高暴露水平(2000天或更长时间)，肌萎缩侧索硬化症的风险是未暴露参与者的2.3倍。相反，ALS的风险与自我报告的住宅或娱乐性铅暴露无关。我们的研究首次使用实验室测量和访谈数据来证明肌萎缩侧索硬化症与铅暴露的关联。探讨饮食对肌萎缩侧索硬化症的影响。尽管一些证据表明氧化应激可能在肌萎缩侧索硬化症中发挥作用，但我们发现几乎没有证据表明抗氧化剂微量营养素具有保护作用。番茄红素摄入量最高四分之一的个体患肌萎缩侧索硬化的风险只有一半。我们没有发现肌萎缩侧索硬化症与饮食中钙或镁的摄入量有关，尽管有研究表明，这些矿物质的低摄入量可能会增加患肌萎缩侧索硬化症的风险。

Aims: To characterize potential associations of ALS with: lead exposure exposure to other neurotoxins, eg, mercury, solvents and pesticides lifestyle factors such as cigarette smoking and diet genetic polymorphisms affecting neurologic function or lead metabolism Accomplishments: Our main focus was on the relationship of ALS with lead exposure. Elevations in lead levels were associated with ALS for both bone and blood. Risk of disease increased 1.7-fold for each unit increase in blood lead, 5.3-fold for each unit increase in patella lead, and 4.2-fold for each unit increase in tibia lead. Lead levels in both cases and controls were nevertheless within the normal range. These results may suggest that chronic exposure even to small elevations in lead levels increases risk of ALS. We also found that risk of ALS was related to self-reported occupational exposure to lead. Risk of ALS was 1.9-fold greater among participants who had ever had a job involving lead exposure, and there was a dose-response for lifetime days of lead exposure. At the highest level of exposure (2000 or more days), risk of ALS was 2.3-fold greater than among unexposed participants. In contrast, risk of ALS was not associated with self-reports of either residential or recreational lead exposure. Our study is the first to use laboratory measurements as well as interview data to demonstrate an association of ALS with lead exposure. We explored the impact of diet on ALS. Although some evidence suggests that oxidative stress may play a role in ALS, we found little evidence for a protective effect of antioxidant micronutrients. Individuals in the highest quartile of lycopene intake had only half the risk of ALS. We found no relationship of ALS to dietary intake of calcium or magnesium although it has been suggested that low intake of these minerals may increase risk of ALS.