Lead exposure as a risk factor for amyotrophic lateral sclerosis.
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 mug/dl increment in blood lead and a 2.3- to 3.6-fold increase for each doubling of bone lead. A polymorphism in the delta-aminolevulinic acid dehydratase gene was associated with a 1.9-fold increase in ALS risk.


CONCLUSIONS
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.
Kamel
F
F
National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. kamel@mail.nih.gov
Umbach
D M
DM
Hu
H
H
Munsat
T L
TL
Shefner
J M
JM
Taylor
J A
JA
Sandler
D P
DP
D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007854:Lead / Q000009:adverse effects* / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016273:Occupational Exposure / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics; D012307:Risk Factors
D007854:Lead; D000623:Porphobilinogen Synthase