Lead And Other Neurotoxins As Risk Factors For ALS

目的：表征ALS与铅暴露的潜在关联：暴露于其他神经毒素，如汞、溶剂和农药，吸烟和饮食等生活方式因素影响神经功能或铅代谢的遗传多态性。骨骼和血液中的铅含量升高与肌萎缩侧索硬化症有关。血铅每增加一个单位，患病风险增加1.7倍；髌骨铅每增加一个单位，患病风险增加5.3倍；胫骨铅每增加一个单位，患病风险增加4.2倍。然而，两例和对照组的铅含量都在正常范围内。这些结果可能表明，长期接触即使是少量的铅水平升高也会增加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。曾经从事过铅接触工作的参与者患ALS的风险高出1.9倍，并且存在终生铅接触天数的剂量反应。在最高暴露水平（2000天或更长时间），ALS的风险比未暴露的参与者高2.3倍。相比之下，ALS的风险与自我报告的居住或娱乐铅暴露无关。我们的研究是第一个使用实验室测量和访谈数据来证明ALS与铅暴露的关联。我们探讨了饮食对ALS的影响。尽管一些证据表明氧化应激可能在ALS中起作用，但我们发现抗氧化微量营养素具有保护作用的证据很少。番茄红素摄入量最高的四分之一个体患ALS的风险只有一半。我们发现ALS与饮食中钙或镁的摄入没有关系，尽管有人认为低摄入这些矿物质可能会增加ALS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.