Effect modification of the association between total cigarette smoking and ALS risk by intensity, duration and time-since-quitting: Euro-MOTOR

J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):33-39. doi: 10.1136/jnnp-2019-320986. Epub 2019 Aug 21.

Abstract

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 (ptrend=0.001) rather than intensity (ptrend=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (ptrend<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.

Keywords: amyotrophic lateral sclerosis; case–control study; pooled analysis; tobacco.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / epidemiology*
  • Case-Control Studies
  • Cigarette Smoking
  • Female
  • Humans
  • Ireland / epidemiology
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects
  • Smoking / epidemiology*
  • Smoking Cessation*
  • Socioeconomic Factors
  • Young Adult