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Exploring causality of the association between smoking and Parkinson's disease

Gallo, Valentina; Vineis, Paolo; Cancellieri, Mariagrazia; Chiodini, Paolo; Barker, Roger A. LU ; Brayne, Carol; Pearce, Neil; Vermeulen, Roel; Panico, Salvatore and Bueno-de-Mesquita, Bas, et al. (2019) In International Journal of Epidemiology 48(3). p.912-925
Abstract

BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a... (More)

BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.

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publication status
published
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keywords
causal inference, cohort study, EPIC, NeuroEPIC4PD, Parkinson’s disease, passive smoking, smoking, smoking patterns
in
International Journal of Epidemiology
volume
48
issue
3
pages
14 pages
publisher
Oxford University Press
external identifiers
  • scopus:85072058871
ISSN
1464-3685
DOI
10.1093/ije/dyy230
language
English
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yes
id
5717d67f-b9c7-4411-a8c6-dd333fa8d233
date added to LUP
2019-09-23 09:21:46
date last changed
2019-11-11 10:52:55
@article{5717d67f-b9c7-4411-a8c6-dd333fa8d233,
  abstract     = {<p>BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking &lt;20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and &gt;30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.</p>},
  author       = {Gallo, Valentina and Vineis, Paolo and Cancellieri, Mariagrazia and Chiodini, Paolo and Barker, Roger A. and Brayne, Carol and Pearce, Neil and Vermeulen, Roel and Panico, Salvatore and Bueno-de-Mesquita, Bas and Vanacore, Nicola and Forsgren, Lars and Ramat, Silvia and Ardanaz, Eva and Arriola, Larraitz and Peterson, Jesper and Hansson, Oskar and Gavrila, Diana and Sacerdote, Carlotta and Sieri, Sabina and Kühn, Tilman and Katzke, Verena A. and van der Schouw, Yvonne T. and Kyrozis, Andreas and Masala, Giovanna and Mattiello, Amalia and Perneczky, Robert and Middleton, Lefkos and Saracci, Rodolfo and Riboli, Elio},
  issn         = {1464-3685},
  keyword      = {causal inference,cohort study,EPIC,NeuroEPIC4PD,Parkinson’s disease,passive smoking,smoking,smoking patterns},
  language     = {eng},
  number       = {3},
  pages        = {912--925},
  publisher    = {Oxford University Press},
  series       = {International Journal of Epidemiology},
  title        = {Exploring causality of the association between smoking and Parkinson's disease},
  url          = {http://dx.doi.org/10.1093/ije/dyy230},
  volume       = {48},
  year         = {2019},
}