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


Journal

International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871

Informations de publication

Date de publication:
01 06 2019
Historique:
accepted: 11 10 2018
pubmed: 22 11 2018
medline: 2 4 2020
entrez: 22 11 2018
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 30462234
pii: 5184917
doi: 10.1093/ije/dyy230
pmc: PMC6659366
doi:

Substances chimiques

Tobacco Smoke Pollution 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

912-925

Subventions

Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

© The Author(s) 2018. Published by Oxford University Press on behalf of the International Epidemiological Association.

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Auteurs

Valentina Gallo (V)

Centre for Primary Care and Public Health, Blizard Institute, Queen Mary University of London, London, UK.
School of Public Health, Imperial College London, London, UK.
Epidemiology and Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK.

Paolo Vineis (P)

School of Public Health, Imperial College London, London, UK.

Mariagrazia Cancellieri (M)

Centre for Primary Care and Public Health, Blizard Institute, Queen Mary University of London, London, UK.
School of Hygiene and Preventive Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Hygiene and Public Health Unit, Department of Public Health, AUSL Imola, Bologna, Italy.

Paolo Chiodini (P)

Medical Statistics Unit, University of Campania 'Luigi Vanvitelli', Naples, Italy.

Roger A Barker (RA)

Institute of Public Health, University of Cambridge, Cambridge, UK.

Carol Brayne (C)

Institute of Public Health, University of Cambridge, Cambridge, UK.

Neil Pearce (N)

Epidemiology and Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK.

Roel Vermeulen (R)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Division of Epidemiology, Institute for Risk Assessment Science, Utrecht University, Utrecht, The Netherlands.

Salvatore Panico (S)

Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.

Bas Bueno-de-Mesquita (B)

School of Public Health, Imperial College London, London, UK.
National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Nicola Vanacore (N)

National Centre for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy.

Lars Forsgren (L)

Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.

Silvia Ramat (S)

Department of Neuroscience, Psychology, Drug Research, and Child Health, University of Florence, Careggi Hospital-University, Florence, Italy.

Eva Ardanaz (E)

Navarra Public Health Institute, IdiSNA, Pamplona, Spain.
CIBER Epidemiology and Public Health, CIBERESP, Madrid, Spain.

Larraitz Arriola (L)

CIBER Epidemiology and Public Health, CIBERESP, Madrid, Spain.
Public Health Department of Gipuzkoa, Basque Government, Vitoria-Gasteiz, Spain.
Biodonostia Research Institute, Neurosciences Area, Hospital Universitario Donostia, Donostia, Spain.

Jesper Peterson (J)

Department of Neurology, Lund University, Lund, Sweden.

Oskar Hansson (O)

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.

Diana Gavrila (D)

CIBER Epidemiology and Public Health, CIBERESP, Madrid, Spain.
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.

Carlotta Sacerdote (C)

Unit of Cancer Epidemiology, Centre for Cancer Prevention (CPO-Piemonte), Turin, Italy.
Human Genetic Foundation (HuGeF), Turin, Italy.

Sabina Sieri (S)

Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Tilman Kühn (T)

Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Verena A Katzke (VA)

Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Yvonne T van der Schouw (YT)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Andreas Kyrozis (A)

Hellenic Health Foundation, Athens, Greece.
First Department of Neurology, University of Athens, Athens, Greece.

Giovanna Masala (G)

Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention, and Clinical Network (ISPRO), Florence, Italy.

Amalia Mattiello (A)

Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.

Robert Perneczky (R)

School of Public Health, Imperial College London, London, UK.
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany.
German Centre for Neurodegenerative Disorders (DZNE), Munich, Germany.
Munich Cluster for System Neurology (SyNergy), Munich, Germany.

Lefkos Middleton (L)

School of Public Health, Imperial College London, London, UK.

Rodolfo Saracci (R)

International Agency for Research on Cancer (IARC), Lyon, France.

Elio Riboli (E)

School of Public Health, Imperial College London, London, UK.

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