{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T01:51:02Z","timestamp":1783389062791,"version":"3.54.6"},"reference-count":24,"publisher":"BMJ","issue":"1","funder":[{"name":"Netherlands ALS Foundation"},{"name":"European Community's Health Seventh Framework Programme","award":["FP7\/2007-2013, grant number 259867"],"award-info":[{"award-number":["FP7\/2007-2013, grant number 259867"]}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["Vici Scheme, JPND (STRENGTH)"],"award-info":[{"award-number":["Vici Scheme, JPND (STRENGTH)"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>We investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case\u2013control studies and explored the independent effects of intensity, duration and time-since-quitting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ALS cases and controls, matched by age, sex and region, were recruited in the Netherlands, Italy and Ireland (*Euro-MOTOR project). Demographics and detailed lifetime smoking histories were collected through questionnaires. Effects of smoking status, intensity (cigarettes\/day), duration (years), pack-years and time-since-quitting (years) on ALS risk were estimated using logistic regression models, adjusting for age, sex, alcohol, education and centre. We further investigated effect modification of the linear effects of pack-years by intensity, duration and time-since-quitting using excess OR (eOR) models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analyses were performed on 1410 cases and 2616 controls. Pack-years were positively associated with ALS risk; OR=1.26 (95% CI: 1.03 to 1.54) for the highest quartile compared with never smokers. This association appeared to be predominantly driven by smoking duration (p<jats:sub>trend<\/jats:sub>=0.001) rather than intensity (p<jats:sub>trend<\/jats:sub>=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (p<jats:sub>trend<\/jats:sub>&lt;0.0001). The eOR decreased with time-since-quitting smoking, until about 10 years prior to disease onset. High intensity smoking with shorter duration appeared more deleterious than lower intensity for a longer duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide further support for the association between smoking and ALS. Pack-years alone may be insufficient to capture effects of different smoking patterns. Time-since-quitting appeared to be an important factor, suggesting that smoking may be an early disease trigger.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2019-320986","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T21:16:47Z","timestamp":1566422207000},"page":"33-39","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Effect modification of the association between total cigarette smoking and ALS risk by intensity, duration and time-since-quitting: Euro-MOTOR"],"prefix":"10.1136","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5662-1971","authenticated-orcid":false,"given":"Susan","family":"Peters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne 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