Research Workplace Exposures and the Risk of Amyotrophic Lateral Sclerosis Fang Fang,1,2 Patricia Quinlan,3 Weimin Ye,2 Marie K. Barber,4 David M. Umbach,5 Dale P. Sandler,1 and Freya Kamel 1 1Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA; 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 3Department of Medicine, Division of Occupational and Environmental Medicine, University of California, San Francisco, California, USA; 4Westat, Durham, North Carolina, USA; 5Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Background : Occupation has been suggested to play a role in amyotrophic lateral sclerosis (ALS) etiology, but detailed information on the importance of specific workplace exposures is lacking. o Bjectivs : Our aim was to assess the relationship between workplace exposures and the risk of ALS and to evaluate potential interactions between these exposures and smoking. Methods : We conducted a case–control study in New England between 1993 and 1996, compris- ing 109 cases and 253 controls who completed a structured interview covering occupations and workplace exposures. Unconditional logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for ALS. Analyses were conducted among the entire study population and after stratification by smoking. r esult : We observed a higher risk of ALS for construction workers excluding supervisors (OR = 2.9; 95% CI, 1.2–7.2) and precision metal workers (OR = 3.5; 95% CI, 1.2–10.5). Self-reported exposures to paint strippers; cutting, cooling, or lubricating oils; antifreeze or coolants; mineral or white spirits; and dry cleaning agents each appeared to be associated with a 60–90% higher risk. Specific chemicals related to a > 50% increase in risk of ALS included aliphatic chlorinated hydro- carbons, glycols, glycol ethers, and hexane. Relative risks associated with these workplace exposures and chemicals were greater among nonsmokers and persisted in mutually adjusted models. c onclusi : Our data suggest that certain occupations and workplace exposures may be associ- ated with increased risk of ALS. These results need to be confirmed in independent populations. k ey words : amyotrophic lateral sclerosis, chemicals, relative risk, risk factors, workplace exposures. Environ Health Perspect 117:1387–1392 (2009). doi:10.1289/ehp.0900580 available via http:// dx.doi.org/ [Online 11 May 2009] Amyotrophic lateral sclerosis (ALS) is a dev- astating neurodegenerative disease of the motor neurons with largely unknown etiol- ogy. Various workplace exposures have been implicated in ALS development, although few of these relationships have been confirmed (Armon 2001; Mitchell 2000; Nelson 1995). For example, some studies found that farm- ers and agriculture workers were at increased risk of ALS (Granieri et al. 1988; Gunnarsson et al. 1991; McGuire et al. 1997), but others did not (Sutedja et al. 2007; Weisskopf et al. 2005a). Inconsistent results also have been noted for the relationship between ALS and military service (Schulte et al. 1996; Sutedja et al. 2007; Weisskopf et al. 2005a, 2005b). We conducted a case–control study in New England in 1993–1996 to assess the associations between workplace exposures and ALS, based on self-reported lifetime occupa- tional history and information on exposure to specific chemical and physical agents. Because an association between formaldehyde and ALS has recently been reported (Weisskopf et al. 2009), we assessed this exposure sepa- rately. We also examined whether the associa- tions between workplace exposures and ALS differed between smokers and nonsmokers, because smoking has been suggested as an independent risk factor for ALS (Fang et al. 2006; Kamel et al. 1999; Nelson et al. 2000; Sutedja et al. 2007; Weisskopf et al. 2004) and because exposure to chemicals found in cigarette smoke might influence the metabo- lism or activity of workplace chemicals. Materials and Methods Patients and controls. Our case–control study has been described in detail elsewhere (Kamel et al. 2002). One of the primary aims of the study was to assess the associations between occupational exposures, including lead, and the risk of ALS. All study participants (cases and controls) were recruited between 1993 and 1996. Sequential ALS cases were recruited from two major referral centers in New England. Board-certified neurologists specializing in motor neuron diseases made diagnoses of ALS based on World Federation of Neurology El Escorial criteria (Brooks 1994). Cases were required to live in New England for at least 50% of the year, to be mentally competent, and to speak English. In total, 71% of eligible cases participated in the study (n = 111). About 85% of the cases were enrolled within 1 year after diagnosis and the remainder within 2 years. Population controls who met the same eligibility criteria as cases and had not been diagnosed with a neurodegenerative disease by a physician were identified through ran- dom telephone screening. Controls were Environmental Health Perspectives • volume 117 | number 9 | September 2009 frequency-matched to cases on sex, age (30–55, 56–65, and 66–80 years), and region within New England (Boston metropolitan area, eastern Massachusetts, and rest of New England). A total of 354 eligible controls were contacted, and 270 (76%) were enrolled in the study, including 256 that completed the entire questionnaire. All study participants provided written informed consent. The study proposal was approved by the institutional review boards of the National Institute of Environmental Health Sciences, Tufts–New England Medical Center, and Brigham and Women’s Hospital. Exposure assessment. A structured interview completed within 1 month of enrollment col- lected information on demographics, lifestyle, and occupational history. Study participants reported all jobs held for at least 2 years since they were 19 years of age, with information on industry name, occupational activity, calendar years when a job was initiated and terminated, and the average working hours per week. Industries and occupations were coded using the 1990 Census Industrial and Occupational Classification Codes (U.S. Bureau of Labor Statistics 2008). We restricted the analyses to occupations held before ALS diagnosis among the cases and 2 years before the interview date among the controls (because all the cases were enrolled within 2 years of diagnosis). Two cases and three controls with missing occupa- tional data for all relevant time periods were excluded, leaving 109 cases and 253 controls in the present analysis. The association between military service (ever served in Army, Air Force, Navy, Marines, Coast Guard, or Armed Forces, branch not Address correspondence to F. Kamel, Epidemiology Branch, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop A3-05, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-1581. Fax: (919) 541-2511. E-mail: kamel@niehs.nih.gov Supplemental Material is available online (doi:10.1289/ehp.0900580.S1 via http://dx.doi.org/). We are grateful to L. Lansdell and K. Catoe for conducting the ALS case–control study. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES49005-15). The authors declare they have no competing financial interests. Received 15 January 2009; accepted 11 May 2009. 1387