Pooling of Prospective Studies of Diet, Lifestyle and ALS

描述(申请人提供)：为了前瞻性地调查饮食和生活方式作为肌萎缩侧索硬化症(ALS)危险因素的作用，我们建议汇集饮食和癌症前瞻性研究的汇集项目(癌症汇集项目)的原始数据，该项目是一个由28项队列研究组成的国际联盟。对散发性肌萎缩侧索硬化症的一些危险因素进行了流行病学研究，主要是在回溯性病例对照研究中：吸烟、接触金属或溶剂、创伤和饮食。然而，研究结果并不一致，可能会有偏差；对长期饮食的回溯性病例对照研究特别容易出现回忆偏差。以前的发现需要在严格的前瞻性研究中得到证实，但ALS的低发病率使前瞻性分析成为一个挑战。现有的联盟是应对这一挑战的独特宝贵资源；我们只需要收集有关肌萎缩侧索硬化症的信息。因此，拟议的项目是一个有效的科学调查的不同寻常的机会，提供了一个独特的机会，以绕过迄今为止ALS流行病学研究的主要局限性--能力差和回溯性设计--希望阐明这种毁灭性和致命疾病的病因。这个项目的饮食目标是研究饮食中脂肪酸、抗氧化剂和类黄酮类的摄入量与患有肌萎缩侧索硬化症的水果和蔬菜之间的关系。非饮食目的是调查身体质量指数(BMI)与体力活动和ALS之间的关系。第二个目标是确认吸烟行为和肌萎缩侧索硬化症风险之间的联系，包括评估是否缺乏包年数、每天吸烟的香烟和戒烟后的时间的剂量反应。此外，将追查从初步分析中可能出现的任何有趣的线索。拟议调查的主要优点是其前瞻性设计和有效利用正在进行的国际研究的现有数据。由于肌萎缩侧索硬化症是一种相对罕见的疾病，对肌萎缩侧索硬化症的前瞻性研究需要非常大的人群和长期的随访，成本相当高。通过利用参与癌症汇集项目的具有良好特征的队列，这些队列已经积累了多年的随访，成本和时间可以被削减到一小部分。从合作队列中获得的独立人口将包括450,657名女性和195,097名男性，自项目开始以来，有超过652人死于肌萎缩侧索硬化症(在整个项目期间，肌萎缩侧索硬化症死亡人数将继续增加)。

DESCRIPTION (provided by applicant): To investigate prospectively the role of diet and lifestyle as risk factors of amyotrophic lateral sclerosis (ALS), we propose to pool the primary data of the Pooling Project of Prospective Studies of Diet and Cancer (Cancer Pooling Project), an international consortium of 28 cohort studies. A number of risk factors for sporadic ALS have been examined epidemiologically, mainly in retrospective case-control studies: smoking, exposure to metals or solvents, trauma, and diet. Findings, however, have been inconsistent and may be subject to bias; retrospective case-control studies of long-term diet are particularly prone to recall bias. Previous findings need to be confirmed in rigorous prospective studies, but the low incidence of ALS makes prospective analyses a challenge. The existing consortium is a uniquely valuable resource for meeting that challenge; we need only collect information on ALS. The proposed project is thus an unusual opportunity for efficient scientific investigation, providing a unique opportunity to circumvent the main limitations of epidemiologic studies of ALS to-date -- poor power and retrospective design -- in the hope to elucidate the etiology of this devastating and fatal disease. The dietary aims of this project are to examine the relation between dietary intake of fatty acids, antioxidants and flavonoids, and fruit and vegetables with ALS. The non-dietary aims are to investigate the association between body-mass index (BMI) and physical activity and ALS. A secondary aim is to confirm the associations reported between smoking behavior and risk of ALS, including evaluating whether there is a lack of a dose- response in pack-years, cigarettes smoked per day and time since quitting smoking. In addition, any interesting leads that may emerge from preliminary analyses will be pursued. The main strengths of the proposed investigation are its prospective design and the efficient use of existing data from ongoing international studies. Because ALS is a relatively rare disease, a prospective investigation of ALS would require very large populations and long periods of follow-up, at a considerable cost. By taking advantage of well characterized cohorts participating in the Cancer Pooling Project that have accumulated many years of follow-up, the cost and time can be cut to a small fraction. The independent population made from the collaborating cohorts will comprise 450,657 women and 195,097 men with over 652 ALS deaths from the outset of the project (ALS deaths will continue to be accrued throughout the project duration).