Abstract
BACKGROUND AND OBJECTIVES: Exposure to lung irritants such as smoking and organic solvents has been associated with increased risk of multiple sclerosis (MS), particularly among genetically susceptible individuals. The aim of this study was to investigate the association between occupational exposure to industrial dust and MS and to assess potential interactions with smoking and HLA-DRB1*15:01. METHODS: We conducted a Swedish population-based case-control study. Patients with incident MS age 16-70 years were consecutively identified by neurologists at 40 clinics (2005-2015). Eligibility criteria for participants were age 16-70 years, residence in Sweden, and a neurologist-confirmed diagnosis of MS according to the McDonald criteria. Controls without MS were randomly sampled from the national population register using density sampling and frequency-matched to cases on age, sex, and residential area. Occupational dust exposure was assessed using questionnaire data. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Additive interactions between dust exposure and smoking and between dust exposure and HLA-DRB1*15:01 were assessed by calculating the attributable proportion (AP) due to interaction. An AP >0 is considered evidence of interaction. RESULTS: The analytic sample included 2,070 participants and 2,899 controls. The mean age at index was 34.4 years for participants and 35.4 years for controls. Women comprised 72.5% of participants and 75.1% of controls. Industrial dust exposure was associated with increased rate of MS (OR 1.30, 95% CI 1.05-1.63), with a dose-response relationship with duration (OR per 1-year exposure 1.03, 95% CI 1.00-1.06). Evidence of additive interactions was observed between dust exposure and smoking (AP 0.32, 95% CI 0.03-0.62) and between dust exposure and HLA-DRB1*15:01 (AP 0.25, 95% CI 0.002-0.52). Participants who smoked, were exposed to dust, and carried the HLA-DRB1*15:01 allele had an 11-fold increased rate of MS (OR 11.1, 95% CI 5.7-21.9), compared with those without any of these risk factors. DISCUSSION: Occupational dust exposure was associated with increased rate of MS, particularly in combination with smoking and HLA-DRB1*15:01, suggesting joint effects of occupational, environmental, and genetic risk factors. The reliance on self-reported occupational histories and potential residual confounding are important limitations. Further studies are warranted to clarify underlying mechanisms and to inform preventive strategies.