AS625 - Environmental and occupational risk factors for ALS: a case control study

Investigator Names and Contact Information

Introduction/Intent

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease (MND) in adults, characterized by degeneration of motor neurons in the brain and spinal cord. The etiology is largely unknown and there is no cure for this devastating disorder. Approximately 90% of ALS is sporadic while the remaining 5%-10% is familial and hereditary. In addition to several genetic mutations identified for familial ALS, there are those also associated with sporadic ALS (SALS). There are also a number of personal, environmental and occupational risk factors associated with increased risk of ALS.

We propose to conduct a nested case control study to examine the potential association of environmental and occupational risk factors and ALS among 180 post-menopausal women who died of ALS identified from the Women’s Health Initiative (WHI) study and 360 matched controls. We will examine specific environmental, occupational and personal risk factors for ALS. Controls will be matched to cases from within the WHI cohort study on year of birth (+/- 1 year), race, and gender. The proposed study will be one of the first to examine suspected neurotoxicants and ambient air pollutants in relation to ALS risk in a large cohort of women with ALS with consideration of smoking and other personal characteristics.

SPECIFIC AIMS:

Specific Aim 1: Evaluate exposure to air toxics based on all residences for each set of ALS cases and controls at the census tract level as risk factors for ALS. ALS cases and controls, matched by age, race, and gender, will be identified from the Women's Health Initiative national study. We will make use of the National-Scale Air Toxics Assessment (NATA) database, compiled by U.S. Environmental Protection Agency (EPA) at the census tract level, for 35 suspected neurotoxicants (e.g., metals, pesticides, solvents) of the 180 total hazardous air pollutants (HAPs) available for the following years: 1996, 1999, 2002, 2005 and 2011. In addition to the aforementioned matching criteria, we will also consider potential confounders such as smoking and occupation. https://www.epa.gov/national-air-toxics-assessment

Specific Aim 2: Evaluate the association of long term environmental exposure to levels of the criteria air pollutant, lead, in ALS cases and age, race and gender matched controls from the Women's Health Initiative national study. Lead exposure and ALS risk has been widely studied but never modeled as a cumulative time weighted concentration using U.S. Environmental Protection Agency (EPA) air quality monitors. The proposed study will link monitored lead levels to ALS cases and controls’ location (residence) over a twenty year period (1993-2016). In addition to the monitors, we can also make use of the TRI inventory (Toxic Release Inventory) which provide a yearly amount of lead emissions for each facility in the US (EPA 2012) (N=2229) as well as location. (https://www.epa.gov/outdoor-air-quality-data/download-daily-data) and (https://www.epa.gov/toxics-release-inventory-tri-program)