Prospective study of chemical exposures and amyotrophic lateral sclerosis

Abstract

Background: Although environmental toxins, including pesticides, are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), no data exist from large prospective investigations. This study assessed the association between exposure to chemicals and risk of ALS in a prospective cohort study.

Methods: The relation between self-report of regular exposure to 11 different chemical classes or x rays and ALS mortality among over 1 million participants in the American Cancer Society's Cancer Prevention Study II was prospectively assessed. Follow-up from 1989 through 2004 identified 617 deaths from ALS among men and 539 among women. Adjusted rate ratios (RR) were calculated using Cox proportional hazards.

Results: The RR for ALS mortality among individuals exposed to pesticides/herbicides compared with that among unexposed individuals was 1.07 (95% CI 0.79 to 1.44), but somewhat higher after excluding those with missing duration of pesticides exposure (RR 1.44; 95% CI 0.89 to 2.31; p = 0.14). A non-significant increase in ALS mortality was found among individuals who reported exposure to formaldehyde (RR 1.34; 95% CI 0.93 to 1.92). Excluding those with a missing duration of formaldehyde exposure, the RR was 2.47 (95% CI 1.58 to 3.86), and there was a strongly significant dose-response relation with increasing years of exposure (p trend = 0.0004).

Conclusions: There was little evidence for any association between pesticides/herbicide exposure and ALS. In contrast, evidence was found, suggesting an increased risk of ALS with formaldehyde exposure. Because of the longitudinal design, this result is unlikely to be due to bias, but it should nevertheless be interpreted cautiously and needs to be verified independently.

Figure 1

Rate ratio of Amyotrophic lateral sclerosis (ALS) mortality by years of reported exposure to formaldehyde adjusted for age, smoking, sex, military service, education, alcohol intake, occupation (farmer, laboratory technician, machine assembler, programmer), vitamin E use, and all other chemical classes, Cancer Prevention Study-II, 1989-2004. The rate ratios are indicated next to the black diamonds, and 95% confidence intervals are indicated by the vertical lines. The number of ALS deaths in each category is listed at the bottom.