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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Valentina Gallo
  • Paolo Vineis
  • Mariagrazia Cancellieri
  • Paolo Chiodini
  • Roger A. Barker
  • Carol Brayne
  • Neil Pearce
  • Roel Vermeulen
  • Salvatore Panico
  • Bas Bueno-de-Mesquita
  • Nicola Vanacore
  • Lars Forsgren
  • Silvia Ramat
  • Eva Ardanaz
  • Larraitz Arriola
  • Diana Gavrila
  • Carlotta Sacerdote
  • Sabina Sieri
  • Tilman Kühn
  • Verena A. Katzke
  • Yvonne T. van der Schouw
  • Andreas Kyrozis
  • Giovanna Masala
  • Amalia Mattiello
  • Robert Perneczky
  • Lefkos Middleton
  • Rodolfo Saracci
  • Elio Riboli
Organisations
External organisations
  • Queen Mary University
  • Imperial College London
  • London School of Hygiene and Tropical Medicine
  • University of Bologna
  • University of Cambridge
  • University Medical Center Utrecht
  • Utrecht University
  • University of Naples Federico II
  • National Institute for Public Health and the Environment (RIVM)
  • University of Malaya
  • Istituto Superiore di Sanità
  • Umeå University
  • University of Florence
  • Health Research Institute of Navarra (IDISNA)
  • CIBER Epidemiology and Public Health (CIBERESP)
  • Basque Government
  • Hospital Universitario Donostia
  • Murcia Regional Health Council
  • Istituto Nazionale dei Tumori
  • German Cancer Research Centre
  • Hellenic Health Foundation, Athens
  • National and Kapodistrian University of Athens
  • Institute for Cancer Research, Prevention and Clinical Network (ISPRO)
  • German Center for Neurodegenerative Diseases (DZNE), Bonn
  • International Agency for Research on Cancer, World Health Organization
  • University of Campania Luigi Vanvitelli
  • Careggi University Hospital
  • Centre for Cancer Epidemiology and Prevention (CPO Piemonte)
  • Human Genetics Foundation (HuGeF)
  • Ludwig-Maximilian University of Munich
  • Munich Cluster for Systems Neurology
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Public Health, Global Health, Social Medicine and Epidemiology

Keywords

  • causal inference, cohort study, EPIC, NeuroEPIC4PD, Parkinson’s disease, passive smoking, smoking, smoking patterns
Original languageEnglish
Pages (from-to)912-925
Number of pages14
JournalInternational Journal of Epidemiology
Volume48
Issue number3
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes