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).
Because ALS is a rare disease, we propose to merge data from a series of international studies to investigate whether diet and lifestyle behaviors are risk factors. Each of the studies included have collected comprehensive information on diet and lifestyle factors, like smoking and body mass index, before the participants had symptoms of their disease. We will use these data to see if any of the factors confer a higher or lower risk of ALS on participants. Finding such associations could aid our understanding of the origins of this disease or translate into a change in the approach to its treatment.