Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study.
BACKGROUND
Results from previous studies on a possible interaction between smoking and Epstein-Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting.


OBJECTIVE
To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS.


METHODS
Within the case-control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale.


RESULTS
Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis ( p = 0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66-1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): -0.98, 95% CI: -2.05-0.15, p = 0.09).


CONCLUSIONS
Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway/The Norwegian Multiple Sclerosis Competence Center, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Kjetil
K
Bjørnevik
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway/The Norwegian Multiple Sclerosis Competence Center, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Trond
T
Riise
Division of Neurology, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden.
Inger
I
Bostrom
Department of Biomedical and Specialist Surgical Sciences, Section of Clinical Neurology, University of Ferrara, Ferrara, Italy.
Ilaria
I
Casetta
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway/The Norwegian Multiple Sclerosis Competence Center, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Marianna
M
Cortese
Department of Biomedical and Specialist Surgical Sciences, Section of Clinical Neurology, University of Ferrara, Ferrara, Italy.
Enrico
E
Granieri
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway/Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
Trygve
T
Holmøy
Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
Margitta T
MT
Kampman
Division of Neurology, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden/Department of Neuroscience/Neurology, Uppsala University, Uppsala, Sweden.
Anne-Marie
AM
Landtblom
Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
Sandra
S
Magalhaes
Department of Biomedical and Specialty Surgical Sciences, Section of Clinical Neurology, University of Ferrara, Ferrara, Italy/Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Maura
M
Pugliatti
Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada/Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Christina
C
Wolfson
The Kristian Gerhard Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway/The Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Kjell-Morten
KM
Myhr
D000328:Adult; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007244:Infectious Mononucleosis / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology*
Epstein–Barr virus; Multiple sclerosis; epidemiology; infectious mononucleosis; risk factors; smoking