Farming and Movement Evaluation Study
Farming and Movement Evaluation Study (FAME)
The Farming and Movement Evaluation (FAME) Study examines the relationship between Parkinson's Disease and exposure to pesticides and other neurotoxicants. The study also examines the connection between the illness and lifestyle factors, skin melanin and polymorphisms in genes involved in xenobiotic metabolism, dopaminergic neurotransmission or xenobiotic-specific membrane transport.
FAME is a case-control study of Parkinson's Disease (PD) nested in the Agricultural Health Study (AHS). The AHS, a cohort study of approximately 90,000 licensed pesticide applicators and their spouses who were recruited in 1993-97, is designed to study the association of cancer and other health outcomes with farm-related exposures. The specific aims of FAME are to examine the relationship of PD to:
- pesticide exposure
- other neurotoxicants, particularly metals
- lifestyle factors including diet, smoking, and caffeine
- skin melanin, to examine racial/ethnic differences
- polymorphisms in genes involved in xenobiotic metabolism, dopaminergic neurotransmission, or xenobiotic-specific membrane transport
All FAME participants have been enrolled; the study includes 114 cases and 384 controls matched by age, gender and state. Suspect cases were identified using information from the AHS, and the diagnosis of PD was verified by consensus of two movement disorder specialists based on an in-home exam, a videotaped movement evaluation and medical records. Controls were a stratified random sample from the remaining cohort, matched to cases by age, sex and state. Exposure was evaluated using data from three complementary sources. The study collaborators used interview information on pesticide use, other exposures and lifestyle already collected in the AHS. In addition, they collected blood samples and samples of house and farm equipment dust for DNA banking and to measure pesticides and metals. Finally, they conducted extensive interviews to obtain additional information on pesticide and other exposures and lifestyle and other risk factors for PD.
This study is one of the first to use prospectively collected exposure information to evaluate the hypothesis that pesticide exposure is related to PD risk. It exploits the unique opportunity provided by the AHS to address this issue in an occupational group defined by pesticide use, combining rigorous methods of case-finding with several complementary methods of exposure assessment.
PD is a progressive movement disorder affecting over 500,000 U.S. residents. The etiology of PD is still unclear. A recent twin study suggested that PD was not primarily a heritable disorder. Genetic susceptibility to environmental exposures involving multiple genes may still play a role: PD has been linked to polymorphisms in several genes, typically involving dopamine neurochemistry or metabolism of xenobiotics.
The etiology of PD likely has an environmental component. Several epidemiologic studies have demonstrated that PD risk is associated with rural living, well water drinking, farming, pesticides and metals. PD risk has also been associated with age, diet, and lifestyle factors including cigarette smoking, which is protective. Epidemiologic and experimental evidence indicates that the pathophysiology of PD likely involves several interacting mechanisms, including mitochondrial dysfunction, oxidative stress, protein aggregation and dysfunction of the ubiquitin-proteasome system. Environmental neurotoxicants likely work through these pathways.