Effect modification of the association between total cigarette smoking and ALS risk by intensity, duration and time-since-quitting: Euro-MOTOR
Open accessAbstract
Background: We investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case–control studies and explored the independent effects of intensity, duration and time-since-quitting. Methods: 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. Results: 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 trend=0.001) rather than intensity (p trend=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (p trend<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. Conclusions: 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.
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Some associations between environmental risk factors and ALS potentially vary by age, sex, and genetic factors.
“with some of the associations potentially varying by age, sex, and genetic factors [11–15].”
From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [15]
The Introduction says environmental exposures may act on genetic predisposition, and the Neurodegeneration discussion reports a somewhat stronger smoking association after excluding cases with a C9orf72 repeat expansion. The Methods say age and sex were adjustment variables, but our copy does not report that the smoking–ALS association varies by either age or sex. No page numbers are available in the indexed passages. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSome observational studies showed a positive association for current smoking but no association for former smoking with ALS risk.
“Some observational studies showed a positive association for current smoking but no association for former smoking [7, 14, 15], while Mendelian Randomization studies have provided evidence for a causal link between smoking and risk for ALS [49].”
From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [15]
The Neurodegeneration section reports a positive association for current smoking (OR 1.47, 95% CI 1.20–1.79). The Results give counts for former smokers, and the Discussion reports declining ALS risk with time since quitting, but the available passages do not establish that former smoking had no association with ALS risk compared with never smoking. No page numbers are provided in our copy. (LLM, conf=0.79)
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Peng, B., Yang, Q., B Joshi, R., Liu, Y., Akbar, M., Song, B.-J., Zhou, S., & Wang, X. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072316 · Cited by 156 · see citing works
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“Some observational studies showed a positive association for current smoking but no association for former smoking [7, 14, 15], while Mendelian Randomization studies have provided evidence for a causal link between smoking and risk for ALS [49].”
Background
- Authors
- Peters, S., Visser, A. E., D'Ovidio, F., Vlaanderen, J., Portengen, L., Beghi, E., Chio, A., Logroscino, G., Hardiman, O., Pupillo, E., Veldink, J. H., Vermeulen, R., & van den Berg, L. H.
- Affiliations
- Utrecht University (NL)
- University Medical Center Utrecht (NL)
- Mario Negri Institute for Pharmacological Research (IT)
- University of Bari Aldo Moro (IT)
- Trinity College Dublin (IE)
- Corresponding author
- Peters, Susan
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2019-08-21
- Volume
- 91
- Issue
- 1
- Pages
- 33-39
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W2969980778
- Cited by
- 33
- References
- 1
- Citations by year
- 2026: 3 · 2024: 9 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 6
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- Netherlands ALS Foundation
- European Community's Health Seventh Framework Programme (FP7/2007-2013, grant number 259867)
- Netherlands Organization for Health Research and Development (Vici Scheme, JPND (STRENGTH))
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- cigarette smoking, amyotrophic lateral sclerosis, pack-years, smoking intensity, smoking duration, time since quitting, effect modification, smoking cessation, neurodegenerative disease risk
- MeSH terms
- Cigarette Smoking, Adult, Aged, Amyotrophic Lateral Sclerosis, Female, Humans, Ireland, Italy, Male, Middle Aged, Netherlands, Risk Factors, Smoking, Socioeconomic Factors, Case-Control Studies, Smoking Cessation, Risk Assessment, Young Adult
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