Pooling of Prospective Studies of Diet, Lifestyle and ALS

描述（由申请人提供）：为了前瞻性地研究饮食和生活方式作为肌萎缩性侧索硬化症（ALS）危险因素的作用，我们建议汇集饮食和癌症前瞻性研究汇集项目（Cancer Pooling Project）的主要数据，这是一个由28项队列研究组成的国际联盟。散发性肌萎缩侧索硬化症的一些危险因素已经进行了流行病学检查，主要是在回顾性病例对照研究中：吸烟、接触金属或溶剂、创伤和饮食。然而，研究结果不一致，可能存在偏见；长期饮食的回顾性病例对照研究尤其容易出现回忆偏差。先前的发现需要在严格的前瞻性研究中得到证实，但ALS的低发病率使得前瞻性分析成为一项挑战。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ALS的信息。因此，拟议的项目是进行有效科学调查的一个不同寻常的机会，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——低功率和回顾性设计——希望阐明这种毁灭性和致命疾病的病因。该项目的饮食目的是研究饮食中脂肪酸、抗氧化剂和类黄酮的摄入以及水果和蔬菜与ALS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风险之间的关联，包括评估是否在包年、每天吸烟和戒烟后的时间上缺乏剂量反应。此外，从初步分析中可能出现的任何有趣的线索都将继续追查。拟议调查的主要优势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，对ALS的前瞻性调查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Cancer Pooling Project的特征明确的队列，积累了多年的随访，可以将成本和时间降低到很小的一部分。从合作队列中组成的独立人口将包括450 657名妇女和195 097名男子，自项目开始以来，死亡人数超过652人（在整个项目期间，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).