Pooling of Prospective Studies of Diet, Lifestyle and ALS

描述（由申请人提供）：为了前瞻性研究饮食和生活方式作为肌萎缩侧索硬化症（ALS）风险因素的作用，我们建议汇总饮食与癌症前瞻性研究汇总项目（癌症汇总项目）的主要数据，该项目是一个由28项队列研究组成的国际联盟。一些散发性ALS的危险因素已经在流行病学上进行了研究，主要是在回顾性病例对照研究中：吸烟，金属或溶剂暴露，创伤和饮食。然而，研究结果是不一致的，可能会受到偏见;回顾性病例对照研究的长期饮食特别容易回忆偏见。以前的研究结果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;我们只需要收集关于ALS的信息。因此，拟议的项目是一个不寻常的机会，有效的科学调查，提供了一个独特的机会，以规避ALS的流行病学研究的主要局限性，到目前为止-穷人的权力和回顾性设计-在希望阐明这种毁灭性的和致命的疾病的病因。本研究旨在探讨肌萎缩侧索硬化症患者膳食中脂肪酸、抗氧化剂、类黄酮及水果蔬菜的摄入与肌萎缩侧索硬化症的关系。非饮食目的是调查身体质量指数（BMI）和体力活动与ALS之间的关系。第二个目的是确认吸烟行为与ALS风险之间的相关性，包括评估是否缺乏包年、每天吸烟和戒烟后时间的剂量反应。此外，还将追踪初步分析中可能出现的任何令人感兴趣的线索。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ALS是一种相对罕见的疾病，因此ALS的前瞻性研究需要非常大的人群和长时间的随访，成本相当高。通过利用参与癌症汇集项目的特征良好的队列，这些队列已经积累了多年的随访，成本和时间可以减少到很小的一部分。从合作队列中获得的独立人群将包括450，657名女性和195，097名男性，从项目开始时起，ALS死亡人数将超过652人（在整个项目期间，ALS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).