Dataset Information

Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England.

ABSTRACT:

Background

Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS).

Objective

To evaluate environmental and occupational exposures as risk factors for sporadic ALS.

Methods

We performed a case-control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness.

Results

Self-reported job- or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI 1.64-3.89). Industries with a higher toxicant exposure potential (construction, manufacturing, mechanical, military, or painting) were associated with an elevated occupational risk (adjusted OR 3.95; 95% CI 2.04-8.30). We also identified increases in the risk of ALS associated with frequent participation in water sports, particularly waterskiing (adjusted OR 3.89; 95% CI 1.97-8.44). Occupation and waterskiing both retained independent statistical significance in a composite model containing age, gender, and smoking status.

Conclusions

Our study contributes to a growing body of literature implicating occupational- and hobby-related toxicant exposures in ALS etiology. These epidemiologic study results also provide motivation for future evaluation of water-body-related risk factors.

SUBMITTER: Andrew AS

PROVIDER: S-EPMC5383428 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England.

Andrew Angeline S AS Caller Tracie A TA Tandan Rup R Duell Eric J EJ Henegan Patricia L PL Field Nicholas C NC Bradley Walter G WG Stommel Elijah W EW

Neuro-degenerative diseases 20170126 2-3

<h4>Background</h4>Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS).<h4>Objective</h4>To evaluate environmental and occupational exposures as risk factors for sporadic ALS.<h4>Methods</h4>We performed a case-control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodeg ...[more]

PMID: 28122372

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Project description:BackgroundAmyotrophic lateral sclerosis (ALS) is linked to ageing and genetic and environmental risk factors, yet underlying mechanisms are incompletely understood. We aimed to evaluate epigenetic age acceleration (EAA), i.e., DNA methylation (DNAm) age acceleration, and its association with ALS case status and survival.MethodsIn this study, we included 428 ALS and 288 control samples collected between 2011 and 2021. We calculated EAA using the GrimAge residual method from ALS and control blood samples and grouped participants with ALS into three ageing groups (fast, normal, slow). We associated EAA with ALS case status and survival, stratified by sex, and correlated it with environmental and biological factors through occupational exposure assessments, immune cell proportions, and transcriptome changes.FindingsParticipants with ALS had higher average EAA by 1.80 ± 0.30 years (p < 0.0001) versus controls. Participants with ALS in the fast ageing group had a hazard ratio of 1.52 (95% confidence interval 1.16-2.00, p = 0.0028) referenced to the normal ageing group. In males, this hazard ratio was 1.55 (95% confidence interval 1.11-2.17, p = 0.010), and EAA was positively correlated with high-risk occupational exposures including particulate matter (adj.p < 0.0001) and metals (adj.p = 0.0087). Also, in male participants with ALS, EAA was positively correlated with neutrophil proportions and was negatively correlated with CD4+ T cell proportions. Pathways dysregulated in participants with ALS with fast ageing included spliceosome, nucleocytoplasmic transport, axon guidance, and interferons.InterpretationEAA was associated with ALS case status and, at least in males, with shorter survival after diagnosis. The effect of EAA on ALS was partially explained by occupational exposures and immune cell proportions in a sex-dependent manner. These findings highlight the complex interactions of ageing and exposures in ALS.FundingNIH, CDC/National ALS Registry, ALS Association, Dr. Randall Whitcomb Fund for ALS Genetics, Peter Clark Fund for ALS Research, Sinai Medical Staff Foundation, Scott L. Pranger ALS Clinic Fund, NeuroNetwork Therapeutic Discovery Fund, NeuroNetwork for Emerging Therapies.

Project description:ImportancePersistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS).ObjectiveTo evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.Design, setting, and participantsCase-control study conducted between 2011 and 2014 at a tertiary referral center for ALS. Cases were patients diagnosed as having definitive, probable, probable with laboratory support, or possible ALS by revised El Escorial criteria; controls were excluded if they were diagnosed as having ALS or another neurodegenerative condition or if they had a family history of ALS in a first- or second-degree blood relative. Participants completed a survey assessing occupational and residential exposures. Blood concentrations of 122 persistent environmental pollutants, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and brominated flame retardants (BFRs), were measured using gas chromatography-mass spectrometry. Multivariable models with self-reported occupational exposures in various exposure time windows and environmental toxin blood concentrations were separately fit by logistic regression models. Concordance between the survey data and pollutant measurements was assessed using the nonparametric Kendall τ correlation coefficient.Main outcomes and measuresOccupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs, PCBs, and BFRs.ResultsParticipants included 156 cases (mean [SD] age, 60.5 [11.1] years; 61.5% male) and 128 controls (mean [SD] age, 60.4 [9.4] years; 57.8% male); among them, 101 cases and 110 controls had complete demographic and pollutant data. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS (odds ratio [OR] = 5.09; 95% CI, 1.85-13.99; P = .002). Military service was also associated with ALS in 2 time windows (exposure ever happened in entire occupational history: OR = 2.31; 95% CI, 1.02-5.25; P = .046; exposure ever happened 10-30 years ago: OR = 2.18; 95% CI, 1.01-4.73; P = .049). A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for 2 OCPs (pentachlorobenzene: OR = 2.21; 95% CI, 1.06-4.60; P = .04; and cis-chlordane: OR = 5.74; 95% CI, 1.80-18.20; P = .005), 2 PCBs (PCB 175: OR = 1.81; 95% CI, 1.20-2.72; P = .005; and PCB 202: OR = 2.11; 95% CI, 1.36-3.27; P = .001), and 1 BFR (polybrominated diphenyl ether 47: OR = 2.69; 95% CI, 1.49-4.85; P = .001). There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood; significant Kendall τ correlation coefficients ranged from -0.18 (Dacthal and "use pesticides to treat home or yard") to 0.24 (trans-nonachlor and "store lawn care products in garage").Conclusions and relevanceIn this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk factors.

Dataset Information

Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England.

Background

Objective

Methods

Results

Conclusions

Publications

Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England.

Similar Datasets

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