Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study

2016 ◽  
Vol 23 (7) ◽  
pp. 1018-1024 ◽  
Author(s):  
Kjetil Bjørnevik ◽  
Trond Riise ◽  
Inger Bostrom ◽  
Ilaria Casetta ◽  
Marianna Cortese ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Population Based ◽  
Pooled Analysis ◽  
Negative Interaction ◽  
Barr Virus ◽  
Increased Risk ◽  
History Of ◽  
Epstein Barr ◽  
Control Study ◽  
Additive Scale

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. Objectives: 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). Conclusion: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.

Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis

2009 ◽  
Vol 15 (4) ◽  
pp. 431-436 ◽  
Author(s):  
TR Nielsen ◽  
K Rostgaard ◽  
J Askling ◽  
R Steffensen ◽  
A Oturai ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Infectious Mononucleosis ◽  
Human Leukocyte ◽  
Epstein Barr Virus Infection ◽  
Leukocyte Antigen ◽  
Barr Virus ◽  
Increased Risk ◽  
History Of ◽  
Epstein Barr ◽  
Barr Virus Infection

Background Both human leukocyte antigen (HLA)-DRB1*15 and Epstein-Barr virus infection presenting as infectious mononucleosis (IM) are recognized as risk factors for multiple sclerosis (MS). However, their combined effect and possible interaction on MS risk is not known. Objective To assess the association between HLA-DRB1*15 and risk of MS in persons with and without IM. Methods We compared the prevalence of DRB1*15 in MS patients with ( n = 76) and without ( n = 1,836) IM with the corresponding distributions in blood donors with ( n = 62) and without ( n = 484) IM histories. This allowed us to estimate the relative risk of MS associated with DRB1*15 in the presence and absence, respectively, of previous IM. We then estimated the interaction between DRB1*15 and IM as the ratio of the two individual odds ratios. Results In IM-naïve individuals, DRB1*15 carried a 2.4-fold (95% confidence interval [CI], 2.0–3.0) increased MS risk. In contrast, among persons with IM history, DRB1*15 was associated with a 7.0-fold (95% CI, 3.3–15.4) increased MS risk. Thus, the MS risk conferred by HLA-DRB1*15 was 2.9 (95% CI, 1.3–6.5)-fold stronger in the presence than in the absence of IM. Combined with previous results, this result indicates that DRB1*15-positive persons with a history of IM may be at a 10.0-fold (95% CI, 6.0–17.9) increased risk of MS compared with persons who are DRB1*15 and IM-naïve. Conclusion DRB1*15 and IM may act in synergy causing MS.

Population attributable fractions and joint effects of key risk factors for multiple sclerosis

2015 ◽  
Vol 22 (4) ◽  
pp. 461-469 ◽  
Author(s):  
IAF van der Mei ◽  
RM Lucas ◽  
BV Taylor ◽  
PC Valery ◽  
T Dwyer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Sun Exposure ◽  
Population Based ◽  
Population Attributable Fractions ◽  
Attributable Fractions ◽  
History Of ◽  
Cns Demyelination ◽  
Control Study ◽  
Additive Scale

Aim: We examined the combined effect of having multiple key risk factors and the interactions between the key risk factors of multiple sclerosis (MS). Methods: We performed an incident case-control study including cases with a first clinical diagnosis of central nervous system demyelination (FCD) and population-based controls. Results: Compared to those without any risk factors, those with one, two, three, and four or five risk factors had increased odds of being an FCD case of 2.12 (95% confidence interval (CI), 1.11–4.03), 4.31 (95% CI, 2.24–8.31), 7.96 (95% CI, 3.84–16.49), and 21.24 (95% CI, 5.48–82.40), respectively. Only HLA-DR15 and history of infectious mononucleosis interacted significantly on the additive scale (Synergy index, 3.78; p = 0.03). The five key risk factors jointly accounted for 63.8% (95% CI, 43.9–91.4) of FCD onset. High anti-EBNA IgG was another important contributor. Conclusions: A high proportion of FCD onset can be explained by the currently known risk factors, with HLA-DR15, ever smoking and low cumulative sun exposure explaining most. We identified a significant interaction between HLA-DR15 and history of IM in predicting an FCD of CNS demyelination, which together with previous observations suggests that this is a true interaction.

scholarly journals Systematic review and meta-analysis of the association between Epstein-Barr virus, Multiple Sclerosis, and other risk factors

2019 ◽  
Author(s):  
Benjamin M Jacobs ◽  
Gavin Giovannoni ◽  
Jack Cuzick ◽  
Ruth Dobson
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Epstein Barr Virus ◽  
Meta Analysis ◽  
Clinically Isolated Syndrome ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Hla Genotype ◽  
Additive Scale

AbstractBackgroundEBV infection is thought to play a central role in the development of Multiple Sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk.ObjectiveTo examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk.MethodsPubmed was searched using the terms “multiple sclerosis” AND “Epstein Barr virus”, “multiple sclerosis” AND EBV, “clinically isolated syndrome” AND “Epstein Barr virus” and “clinically isolated syndrome” AND EBV. All abstracts were reviewed for possible inclusion.Results262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (AP 0.48, p<1×10−4; RERI 3.84, p<5×10−3; S 1.68, p=0.06). Previous IM was associated with increased OR of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR 2.76) but not low anti-EBV antibodies (OR 1.16). No interaction between EBV and risk factors was found on a multiplicative scale.ConclusionsEBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.

Assessing interactions between HLA-DRB1*15 and infectious mononucleosis on the risk of multiple sclerosis

2013 ◽  
Vol 19 (10) ◽  
pp. 1355-1358 ◽  
Author(s):  
Giulio Disanto ◽  
Carolina Hall ◽  
Robyn Lucas ◽  
Anne-Louise Ponsonby ◽  
Antonio J Berlanga-Taylor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Infectious Mononucleosis ◽  
Additive Model ◽  
Causal Process ◽  
Case Control Studies ◽  
Logistic Regression Models ◽  
Gene Environment ◽  
Increased Risk ◽  
History Of ◽  
Additive Scale

Gene–environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). Individuals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92–10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79–2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59–2.59; excess risk due to interaction=3.30, 95%CI=0.47–6.12; attributable proportion due to interaction=45%, 95% CI=22–68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene–environment interactions on both a multiplicative and additive scale.

scholarly journals Shedding light on the link between early life sun exposure and risk of multiple sclerosis: results from the EnvIMS Study

2018 ◽  
Vol 48 (4) ◽  
pp. 1073-1082 ◽  
Author(s):  
Sandra Magalhaes ◽  
Maura Pugliatti ◽  
Trond Riise ◽  
Kjell-Morten Myhr ◽  
Antonio Ciampi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Latent Class ◽  
Sun Exposure ◽  
Sun Protection ◽  
Population Based ◽  
Accumulation Model ◽  
Increased Risk ◽  
Analytical Strategies ◽  
Increasing Risk ◽  
Control Study

Abstract Background Lower levels of sun exposure in childhood have been suggested to be associated with increased risk of multiple sclerosis (MS). In this paper we extend previous work, using two novel analytical strategies. Methods Data collected in the Environmental risk factors In MS (EnvIMS) study, a case-control study with MS cases and population-based controls from Canada, Italy and Norway, were used. Participants reported on sun exposure behaviours for 5-year age intervals from birth; we focused on the first three age intervals (≤15 years). We compared two life course epidemiology conceptual models, the critical period and the accumulation model. We also used latent class analysis to estimate MS risk for different latent sun exposure behaviour groups. Results The analyses included 2251 cases and 4028 controls. The accumulation model was found to be the best model, which demonstrated a nearly 50% increased risk of MS comparing lowest reported summer sun exposure with highest [risk ratio (RR) = 1.47 (1.24, 1.74)]. The latent sun exposure behaviour group, characterized by low sun exposure during summer and winter and high sun protection use, had the highest risk of MS; a 76% increased risk as compared with the group with high sun exposure and low sun protection use [RR = 1.76 (1.27, 2.46)]. Conclusions Our analyses provide novel insights into the link between sun exposure and MS. We demonstrate that more time indoors during childhood and early adolescence is linked with MS risk, and that sun protection behaviours in those who spend most time indoors may play a key role in increasing risk.

scholarly journals Dietary Inflammatory Index and Risk of Multiple Sclerosis in a Case-Control Study from Iran

2016 ◽  
Vol 47 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Nitin Shivappa ◽  
James R. Hebert ◽  
Maryam Behrooz ◽  
Bahram Rashidkhani
Keyword(s):  
Multiple Sclerosis ◽  
Case Control Study ◽  
Continuous Variable ◽  
Case Control ◽  
Dietary Inflammatory Index ◽  
Logistic Regression Models ◽  
Inflammatory Index ◽  
Increased Risk ◽  
History Of ◽  
Control Study

Background: Diet and inflammation have been suggested to be important risk factors for multiple sclerosis (MS). Objectives: In this study, we examined the ability of the dietary inflammatory index (DII) to predict MS in a case-control study conducted in Iran. Methods: This study included 68 MS cases and 140 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Logistic regression models were used to estimate ORs adjusted for age, energy, sex, body mass index, season of birth, rubella history, history of routine exercise before MS, smoking and history of consumption of cow's milk in the first 2 years of life. Results: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of MS, with the DII being used both as a continuous variable (ORcontinuous 1.66; 95% CI 1.19-2.31; 1 unit increase corresponding to ≈15% of its range in the current study) and a categorical variable (ORDII (>1.43 vs.≤1.43) 2.68; 95% CI 1.15-6.26). Conclusions: These results indicate that a pro-inflammatory diet is associated with increased risk of MS.

EBNA-1 reactivity and HLA DRB1*1501 as statistically independent risk factors for multiple sclerosis: a case-control study

2008 ◽  
Vol 14 (8) ◽  
pp. 1120-1122 ◽  
Author(s):  
P Sundström ◽  
L Nyström ◽  
E Jidell ◽  
G Hallmans
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Case Control Study ◽  
Multivariate Logistic Regression Analysis ◽  
Human Leukocyte ◽  
Case Control ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr ◽  
Control Study

Objectives and methods The interaction between the two best documented risk factors (human leukocyte antigen [HLA] class II [DRB1*1501 positivity] and Epstein-Barr virus [elevated Epstein-Barr nuclear antigen 1 (EBNA-1) antibody reactivity]) for multiple sclerosis (MS) was studied in a case-control study of biobank samples from 109 MS cases and 212 matched referents. Results Multivariate logistic regression analysis showed that both were statistically significant in both sexes. HLA DRB1*1501-positive referents had higher EBNA-1 reactivity than HLA-negative referents. Less EBNA-1 reactivity was required to increase the MS risk in HLA DRB1*1501-positives than in HLA-negatives. Conclusion We suggest that HLA DRB1*1501-positive individuals have an increased vulnerability to EBV-induced autoimmunity.

scholarly journals Thyroid disorders and breast cancer risk in Asian population: a nationwide population-based case–control study in Taiwan

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e020194 ◽  
Author(s):  
Chien-Hsiang Weng ◽  
Yi-Huei Chen ◽  
Ching-Heng Lin ◽  
Xun Luo ◽  
Tseng-Hsi Lin
Keyword(s):  
Breast Cancer ◽  
Index Date ◽  
Case Control Study ◽  
Asian Population ◽  
Population Based ◽  
Case Control ◽  
Thyroid Disorders ◽  
Increased Risk ◽  
History Of ◽  
Control Study

ObjectiveTo evaluate whether hyperthyroidism or hypothyroidism increases the risk of subsequent breast cancer in an Asian population.DesignNationwide population-based case–control study.SettingAll healthcare facilities in Taiwan.ParticipantsA total of 103 466 women (mean age 53.3 years) were enrolled.Methods51 733 adult women with newly diagnosed primary breast cancer without a previous cancer history between 2006 and 2011 were identified and included in our study. 51 733 women with no cancer diagnosis prior to the index date were age matched as controls. Diagnosis of hyperthyroidism or hypothyroidism prior to the diagnosis of breast cancer or the same index date was identified, age, histories of thyroid disease treatment, oestrogen use and radioactive iodine treatment were adjusted.Main outcome measuresTo identify risk differences in developing breast cancer among patients with a medical history of hyperthyroidism or hypothyroidism.ResultsThere was a significantly increased risk of breast cancer in women with hyperthyroidism under the age of 55 years (age <45: OR 1.16, P=0.049; age 45–55: OR 1.15, P=0.019). Patients with hypothyroidism also showed an increased risk of breast cancer (OR 1.19, P=0.029) without statistical significance after stratification by age group (age <45, 45–55, >55 years). Treatment for thyroid disorders did not alter the association in subgroup analyses (P=0.857; 0.262, respectively).ConclusionsAsian women under 55 years of age with history of hyperthyroidism have a significantly increased risk of breast cancer regardless of treatment. Women with history of hypothyroidism may also have an increased risk.

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