Pesticide exposure and amyotrophic lateral sclerosis
Highlights
► Pesticide exposure and amyotrophic lateral sclerosis. ► In a meta-analysis of 8 studies, ALS was associated with general pesticide exposure. ► In an agricultural cohort, ALS was associated with organochlorine insecticides. ► Specific pesticides associated with ALS were aldrin, dieldrin, DDT, and toxaphene.
Introduction
ALS is a rapidly progressive neurodegenerative disease affecting motor neurons in the brain and spinal cord, with symptoms including muscular weakness, spasticity, and hyperreflexia. The condition is rare, with an annual incidence of 1–2 per 100,000; incidence is greater in men and increases with age.
The etiology of ALS is not well understood. Approximately 10% of ALS cases have a family history of ALS, likely involving genetic factors. Environmental factors including metals, organic solvents, and pesticides may also contribute to ALS (Sutedja et al., 2009). Exposure to pesticides as a group has been explicitly evaluated in seven case–control studies (Bonvicini et al., 2010, Chancellor et al., 1993, Deapen and Henderson, 1986, Gunnarsson et al., 1992, McGuire et al., 1997, Morahan and Pamphlett, 2006, Savettieri et al., 1991) and one cohort study (Weisskopf et al., 2009); exposure was generally associated with increased risk in the case–control studies although the relationship was not always statistically significant. None of these studies evaluated the role of specific pesticides in ALS etiology.
To summarize existing findings, we conducted a meta-analysis of published studies of ALS and exposure to pesticides as a group. We then evaluated the association of ALS with specific pesticides, using data from the Agricultural Health Study (AHS), a cohort of licensed pesticide applicators and their spouses. Our study provides the first analytic evaluation of the role of specific pesticides in ALS.
Section snippets
Exposure to pesticides as a group: meta-analysis of published studies
We searched for epidemiologic studies of ALS and pesticide exposure in Medline through December 31, 2011, using the MeSH terms “amyotrophic lateral sclerosis,” “motor neuron disease,” and “pesticides.” We also searched the bibliographies of retrieved articles. All identified case–control and cohort studies with information on pesticide use were included in the analysis (Bonvicini et al., 2010, Chancellor et al., 1993, Deapen and Henderson, 1986, Gunnarsson et al., 1992, McGuire et al., 1997,
Results
Studies included in the meta-analysis (Table 1, Fig. 1) evaluated occupational exposure to pesticides as a group, usually with some minimal criterion forever use, e.g., regular use and/or use for some minimal period. Relative risks for pesticide use ranged from 1.1 to 4.7. We saw little evidence of heterogeneity among the seven case–control studies (p > 0.8); the summary OR for pesticide use was 2.2 (95% CI, 1.5–3.3). Inclusion of the cohort study, which introduced some heterogeneity (p = 0.17),
Discussion
We found that ALS risk was associated with use of OCs, pyrethroids, herbicides, and fumigants but not other pesticide classes. Four specific OCs were also associated with ALS risk: aldrin, dieldrin, DDT, and toxaphene. Although not statistically significant, these associations provide leads for further investigation. Results were not materially changed by adjustment for potential confounders including smoking or head injury, which may be risk factors for ALS (Chen et al., 2007, Schmidt et al.,
Conclusions
Our meta-analysis suggests that ALS risk may be associated with use of pesticides as a group, and our analysis of AHS data points to OC use in particular. The latter results are novel but are based on a small number of cases and require replication in other populations.
Conflicts of interest
The authors declare that there are no conflicts of interest.
Acknowledgments
The AHS was conducted by the University of Iowa (Iowa Field Station: Drs. C. Lynch and E. Heywood) and Battelle Inc. (North Carolina Field Station: C. Knott and M. Hayslip); central data coordination was provided by Westat (K. Torres, S. Legum, and M. Dunn). The study was supported by the intramural research program of the NIH, NIEHS (Z01-ES049005 and Z01-ES049030) and NCI (Z01-CP010119).
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