Dataset Information

Joint and interactive effects between health comorbidities and environmental exposures in predicting amyotrophic lateral sclerosis.

ABSTRACT:

Background

Amyotrophic lateral sclerosis (ALS) is a rare yet devastating neurodegenerative condition. The mechanisms leading to ALS are most certainly complex and likely involve a joint contribution of several factors with possible synergistic or antagonistic interactions. To provide a better understanding of the association between non-genetic factors and ALS, we evaluated the joint exposure to multiple health and environmental factors linked with ALS in our previous studies, also screening for high-dimensional interactions.

Methods

We used data from a nested case-control study within the Danish population, with 1086 ALS cases from 1982 to 2009, jointly investigating 4 hospital-based diagnoses - diabetes, obesity, physical/stress trauma, cardiovascular disease (CVD) during 1977-2009; and 4 environmental exposures - lead, formaldehyde, diesel exhaust, and solvents, assessed from individual occupational history. All covariates were evaluated as ever/never exposed, and we used targeted machine learning techniques to screen for important joint predictors and interactions. These were then evaluated in a final logistic regression model adjusting for potential confounders (age, SES, geography). All analyses were stratified by sex.

Results

Among men, trauma and solvents were associated with higher odds of ALS (OR = 1.55, 95% CI: 1.08-2.23; OR = 1.49, 95% CI: 1.17-1.89, respectively), and presented a negative interaction (OR = 0.49, 95% CI: 0.30-0.80). A positive diesel/CVD interaction was observed (OR = 1.56, 95% CI: 0.94-2.60). Among women, solvents, trauma, lead, and CVD were associated with higher odds of ALS, and a negative lead/solvents interaction was documented (OR = 0.52, 95% CI: 0.42-0.63).

Conclusions

This study is one of the first attempts to evaluate joint and interactive effects of multiple risk factors on ALS, identifying potential synergistic and antagonistic mechanisms.

SUBMITTER: Bellavia A

PROVIDER: S-EPMC7736520 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IMPORTANCE:Persistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS). OBJECTIVE:To evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan. DESIGN, SETTING, AND PARTICIPANTS:Case-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 ? correlation coefficient. MAIN OUTCOMES AND MEASURES:Occupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs, PCBs, and BFRs. RESULTS:Participants 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 ? 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 RELEVANCE:In this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk factors.