With the exception of some rare familial forms of the disease, the cause of amyotrophic lateral sclerosis (ALS; motor neuron disease) is unknown (Bruijn et al ., 2004). Although 90–95% of ALS cases are apparently sporadic, SOD1 gene mutations with low penetrance (Cudkowicz et al ., 1997; Anderson et al ., 1997; Shaw et al ., 1998; Al-Chalabi et al ., 1999; Orrell et al ., 1999; Andersen et al ., 2003; Majoor-Krakauer et al ., 2003; Nogales-Gadea et al ., 2004) and other gene variants or mutations may contribute to the population risk (Al-Chalabi et al ., 1999; Mitchell, 2000; Lambrechts et al ., 2003; Majoor-Krakauer et al ., 2003). Advances in understanding the molecular basis of neurodegenerative diseases point clearly to the importance of genetic factors in conditions that until recently we took to be determined mainly, if not solely, by environmental factors, for example, Alzheimer's disease and Parkinson's disease. Genetic predisposing factors may, of course, require an environmental trigger to activate disease processes. There has been no shortage of epidemiological research into ALS attempting to identify a link between ALS and trauma, exposure to toxins, physical activity and a variety of other possible risk factors (Mitchell, 2000; Worms, 2001; Armon, 2003 a , b ). However, the only really consistent epidemiological risk factors for ALS are increasing age, male sex and a family history of ALS (Kurtzke, 1991; Mitchell, 2000; Worms, 2001; Armon, 2003a), although cigarette smoking may also be a risk factor (Nelson et al ., 2000; Armon, 2003 a ; Weisskopf et al ., 2004). Even in Guam, where a restricted population with high risk of developing ALS has been under intense (albeit intermittent) scrutiny for over 50 years, controversy …
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