In this issue of the journal, Steenland et al1 address the possible toxic effects of polychlorinated biphenyls (PCBs) on neurodegenerative diseases. Evidence from animal and cell studies suggest that some pesticides can cause selective degeneration that resembles Parkinson disease.2 However, the role of PCBs is poorly understood. PCBs can cause oxidative stress and disrupt neuronal function by inhibiting dopamine uptake into synaptic vesicles, thus mechanistically linking them to Parkinson disease.3,4 Environmental toxins also may contribute to motor neuron demise in amyotrophic lateral sclerosis (ALS), with more equivocal links to Alzheimer dementia.5
Epidemiologists studying toxic agents and neurodegenerative diseases have been hampered by at least 2 factors. One is the lack of disease registries that could enable population-based case–control studies, and another is the lack of large cohort studies with extensive occupational or environmental exposure information and enough well-characterized cases.
Steenland and colleagues make a laudable effort with this first occupational cohort study of workers highly exposed to PCBs. The authors used state-of-the-science exposure assessment, including the use of biomarker data to inform a job–exposure matrix. Unfortunately, they had to rely on mortality information for assessing outcomes. As the authors note, death certificates severely underreport Parkinson disease and may not perform much better for Alzheimer disease.
Ideally, a cohort study of neurodegenerative diseases would maintain procedures to identify and phenotypically characterize incident cases. This is labor- and cost-intensive and presents a burden to study participants. In retrospective studies, it is usually is not possible. Even though the authors were able to combine 3 cohorts of PCB workers, the number of cases identified was too small for internal comparisons.
Also, the study leaves readers and the authors wondering why the positive findings are limited to female workers, even though Parkinson disease and ALS generally affect men more commonly.6,7 A possible answer might lie in the contributions of gene–environment interactions, which have been widely discussed and will have to be taken into account in future studies.
Finally, this study reminds us that for relatively rare diseases, human research will continue to suffer from small numbers of cases in any single study. Data pooling across population-based studies with adequate exposure assessment will be needed to advance this field. Steenland et al make 2 good steps in this direction—one by their occupational analysis and the other by pooling several cohorts to create the study sample in the first place.
ABOUT THE AUTHOR
BEATE RITZ is a physician with doctorates in medical sociology and epidemiology. Her research specialty is environmental and occupational health, and her research has included the study of pesticide exposure and Parkinson disease. She has served on the faculty at the UCLA School of Public Health since 1995.
1. Steenland K, Hein MJ, Cassinelli RT II, et al. Polychlorinated biphenyls and neurodegenerative disease mortality in an occupationally exposed cohort. Epidemiology
2. Betarbet R, Sherer TB, MacKenzie G, et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci
3. Mariussen E, Morch Andersen J, Fonnum F. The effect of polychlorinated biphenyls on the uptake of dopamine and other neurotransmitters into rat brain synaptic vesicles. Toxicol Appl Pharmacol
4. Lee DW, Opanashuk LA. Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury. Neurotoxicology
5. Brown RC, Lockwood AH, Sonawane BR. Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspect
6. Wooten GF, Currick J, Bovbjerg VE, Lee JK, Patrie J. Are men at greater risk for Parkinson's disease than women? J Neurol Neurosurg Psychiatry
7. Logroscino G, Beghi E, Zoccolella S, et al. Incidence of amyotrophic lateral sclerosis in southern Italy: a population based study. J Neurol Neurosurg Psychiatry