Clinical and Lifestyle Factors and Risk of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods: We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results: We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19–5.72), electric shock (OR = 2.09, 95% CI 0.62–7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73–2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88–2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12–0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions: Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk.

Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study

“…We designed a population-based case-control study to investigate the role of environmental risk factors in ALS etiology. Study methods have been already described in detail [18]. We recruited the ALS cases diagnosed in the period 2008-2011 in Catania, Modena, and Reggio Emilia provinces, and in the period 2002-2012 in Novara province.…”

Reply to Comment on “Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study”

“…In particular, the external validity of the findings of our or other studies may be influenced by the genetic background of the study participants, i.e., by the inclusion of ALS patients carrying specific gene mutations and/or the familial form of the disease, since these subjects may carry specific susceptibilities to chemicals [6,7]. Finally, we strongly agree that the environmental risk factors of ALS, and the exposure to chemicals, particularly including heavy metals [8,9] and selenium [10], as well as other physical and biological factors [11][12][13][14], definitely warrant further investigations, also taking into account the possible interactions between them, to be assessed through advanced data analysis tools [5,15,16].…”

Is Chronic Exposure to Raw Water a Possible Risk Factor for Amyotrophic Lateral Sclerosis? A Pilot Case-Control Study

“…The most robust association evidenced in our study is the one between ALS and raw water use, which is expected to be higher in rural areas and small municipalities ( Table 3 ). Recently, Filippini et al [ 19 ] in a study conducted in Italy on 95 cases and 135 controls, suggest an association, although not significant, between well water consumption for drinking water and ALS risk in the Northern Italian population (OR = 3.33, 95% CI: 0.31–35.69) but not in Southern Italy, where a stronger association with ALS risk was found with current well water consumption for irrigation (OR = 1.74, 95% CI: 0.18–17.21). We observed a not statistically significant association in this study as well, between well water consumption and ALS.…”

“…It is well known that untreated water could be a source for several potential neurotoxic factors: mycotoxins, cyanobacteria, fertilizers or pesticides, and other substances (e.g., metals or solvents) for which many epidemiological studies have highlighted associations with neurotoxic effects and consequent higher incidence of ALS [ 13 , 14 , 20 , 38 , 39 , 40 ]. Filippini et al [ 19 ] observed an odds ratio of 1.95 (95% CI: 0.88–4.36) for use of herbicides in gardening associated with ALS risk while results on pesticide utilization offered little support of increased ALS risk (OR = 1.15, 95% CI: 0.56–2.39). Furthermore, a meta-analysis [ 41 ] highlighted a significant association between pesticide exposure and risk of ALS (OR = 1.88, 95% CI: 1.36–2.61).…”

“…Although a rural residence itself does not give rise to a statistically significant risk of ALS, subjects chronically exposed to a high concentration of pesticides in agricultural settings show a higher risk for ALS than the general population [ 16 , 17 , 18 ]. Recently, in a rural context, exposure to grass and well water for private use has been considered as a key factor in ALS onset, suggesting a high concentration of agricultural chemicals, neurotoxic factors, or mycotoxins as potential etiology of sporadic ALS [ 19 , 20 , 21 ]. Finally, in a case-control study in New England, with 295 patients and 225 controls, patients reported having lived full-time within two miles of a water body more frequently than did controls (OR 1.59) [ 22 ].…”