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Abstract
Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p < 0.0001) but was not associated with occupational exposure to either lead or ACs. Conclusions: Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.
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Acknowledgments
We are grateful for the study P-ALS and their families and siblings, as well as the control participants for their time and interest in the study. We are very appreciative of the encouragement and strong support extended to our research by the ATSDR/CDC study team, Judith Smith, PhD, Wendy Kaye, PhD, and other colleagues. The CDC Contract (200-2013-568886 and R01TS000243 to HM) and MDA Wings Over Wall Street fund supported this project. We acknowledge the late Ray Goetz, PhD, Columbia University, who performed the early statistical analyses. RTI International, NC (Thomas Duffy, Senior Director) oversaw the service that identified matched controls. Dr. Daragh Heitzman, Texas Neurology; Dr. Eric Sorenson, Mayo Clinic Rochester; Dr. Björn Oskarsson, Mayo Clinic Jacksonville; and Dr. J Americo M. Fernandes, University of Nebraska assisted with participant recruitment at their ALS Centers. Jessica Singleton, BA, Brittany McHale, LCSW, Camila Ibagon, BS, and Marie-France Likanje, MA assisted with conducting structured interviews and data entry. Irina Gurvich, MS prepared the biosamples in the Biomarkers Laboratory supported by ES009089, and Iryna Sirosh MS and Qiao Wang analyzed urinary oxidative stress markers. Saliva DNA was prepared by the Genome Center, Department of Neurology, and C9crf72 repeats (only in ALS participants) were processed and analyzed by Ali Naini, PhD, Pathology, Columbia University. Georgia Christodoulou, MA, University of Southern California, assisted in editing the manuscript. Cassandra Telerico, PhD, Cleveland Clinic, edited the final manuscript.
Disclosure statement
The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of ATSDR, CDC, and/or the Department of Health and Human Services (HHS). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
Author contributions
All authors contributed to the manuscript, including assisting in the planning stages, grant preparation, data collection, data analyses, interpretation, writing the draft, and approving the final manuscript.