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Lead exposure as a risk factor for Amyotrophic Lateral Sclerosis.

Kamel R; Umbach DM; Hu H; Munsat TL; Shefner JM; Taylor JA; Sandler DP

Neurodegener Dis 2005 Jan; 2(3-4):195-201

https://doi.org/10.1159/000089625

20057245

Background: The etiology of amyotrophic lateral sclerosis (ALS) likely involves an environmental component. We qualitatively assessed literature on ALS and lead exposure. Problems of study design make case reports and studies of lead in blood or tissues difficult to interpret. Most previous case-control studies found an association of ALS with self-reported occupational exposure to lead, with increased risks of 2- to >4-fold. However, these results may have been affected by recall bias. Objective: To address inconsistencies among published reports, we used both lead biomarkers and interview data to assess lead exposure, and we evaluated the role of genetic susceptibility to lead. Methods: We conducted a case-control study in New England in 1993-1996 with 109 ALS cases and 256 population-based controls. We measured blood and bone lead levels, the latter using X-ray fluorescence, and interviewed participants regarding sources of lead exposure. Results: In our study, ALS was associated with self-reported occupational lead exposure, with a dose response for cumulative days of exposure. ALS was also associated with blood and bone lead levels, with a 1.9-fold increase in risk for each µg/dl increment in blood lead and a 2.3- to 3.6-fold increase for each doubling of bone lead. A polymorphism in the d-aminolevulinic acid dehydratase gene was associated with a 1.9-fold increase in ALS risk. Conclusion: These results, together with previous studies, suggest that lead exposure plays a role in the etiology of ALS. An increase in mobilization of lead from bone into blood may play a role in the acute onset of disease.

Etiology; Environmental exposure; Lead; Exposure levels; Risk factors; Blood; Case control studies; Biomarkers; Genetics; Bone structure; X-rays; X-ray fluorescence analysis; Diseases; Author Keywords: Amyotrophic lateral sclerosis; Epidemiology; Lead exposure; Environment

Freya Kamel, PhD, MPH, Epidemiology Branch, National Institute of Environmental Health Sciences PO Box 12233, MD A3-05, Research Triangle Park, NC 27709

NDEIA6

7439-92-1

20050101

Journal Article

kamel@mail.nih.gov

Grant

2005

Grant-Number-T42-CCT-122961

3-4

1660-2854

Neurodegenerative Diseases

MA; NC; NY

Harvard School of Public Health