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

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Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction

Multiple Sclerosis Journal ◽

10.1177/1352458509102459 ◽

2009 ◽

Vol 15 (5) ◽

pp. 563-570 ◽

Cited By ~ 61

Author(s):

JL Dickinson ◽

DI Perera ◽

AF van der Mei ◽

A-L Ponsonby ◽

AM Polanowski ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Vitamin D Receptor ◽

Significant Interaction ◽

Important Determinant ◽

Sun Exposure ◽

Population Based ◽

Vdr Gene ◽

Increased Risk ◽

Group 2

Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based sample where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A > G), rs10735810 ( Fok1T > C), or rs731236 ( Taq1C > T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.

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High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women

Multiple Sclerosis Journal ◽

10.1177/1352458512436596 ◽

2012 ◽

Vol 18 (9) ◽

pp. 1334-1336 ◽

Cited By ~ 194

Author(s):

Anna K Hedström ◽

Tomas Olsson ◽

Lars Alfredsson

Keyword(s):

Multiple Sclerosis ◽

Body Mass ◽

High Body Mass Index ◽

Population Based ◽

Normal Weight ◽

Preventive Strategy ◽

Swedish Population ◽

Obesity Epidemic ◽

Increased Risk ◽

Control Study

In a Swedish population-based case-control study (1571 cases, 3371 controls), subjects with different body mass indices (BMIs) were compared regarding multiple sclerosis (MS) risk, by calculating odds ratios (OR) with 95% confidence intervals (95% CI). Subjects whose BMI exceeded 27 kg/m2 at age 20 had a two-fold increased risk of developing MS compared with normal weight subjects. Speculatively, the obesity epidemic may explain part of the increasing MS incidence as recorded in some countries. Measures taken against adolescent obesity may thus be a preventive strategy against MS.

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

Multiple Sclerosis Journal ◽

10.1177/1352458516671028 ◽

2016 ◽

Vol 23 (7) ◽

pp. 1018-1024 ◽

Cited By ~ 11

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.

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

Multiple Sclerosis Journal ◽

10.1177/1352458515594040 ◽

2015 ◽

Vol 22 (4) ◽

pp. 461-469 ◽

Cited By ~ 37

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.

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Faculty Opinions recommendation of Increased risk of multiple sclerosis following herpes zoster: a nationwide, population-based study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11561956.12616054 ◽

2011 ◽

Author(s):

Mark Doherty

Keyword(s):

Multiple Sclerosis ◽

Herpes Zoster ◽

Population Based ◽

Population Based Study ◽

Increased Risk

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Estimating the Marginal Causal Effect of Fish Consumption during Adolescence on Multiple Sclerosis: A Population-Based Incident Case-Control Study

Neuroepidemiology ◽

10.1159/000487640 ◽

2018 ◽

Vol 50 (3-4) ◽

pp. 111-118 ◽

Cited By ~ 9

Author(s):

Ibrahim Abdollahpour ◽

Saharnaz Nedjat ◽

Mohammad Ali Mansournia ◽

Mohammad Ali Sahraian ◽

Jay S. Kaufman

Keyword(s):

Multiple Sclerosis ◽

Fish Consumption ◽

Case Control Study ◽

Causal Effect ◽

Population Based ◽

Case Control ◽

Incident Case ◽

Control Study

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Multiple developmental pathways underlying conduct problems: A multitrajectory framework

Development and Psychopathology ◽

10.1017/s0954579420001650 ◽

2020 ◽

pp. 1-10

Author(s):

Jules R. Dugré ◽

Stéphane Potvin

Keyword(s):

Conduct Disorder ◽

Conduct Problems ◽

Latent Class ◽

Population Based ◽

Anxiety Symptoms ◽

Behavioral Approach ◽

Parameter Estimates ◽

Childhood And Adolescence ◽

Increased Risk ◽

Psychological Features

Abstract In the past decades, there has been an overemphasis of a descriptive/behavioral approach to study conduct disorder. In an equifinal perspective, we aimed to examine the developmental multitrajectory groups of psychological features (irritability, interpersonal callousness, hyperactivity/impulsivity, and depressive–anxiety symptoms) and their associations with conduct problems. In a population-based cohort (n = 1,309 participants followed from 5 months to 17 years old), latent-class growth analysis was performed for each psychological feature to identify a two-trajectory model (from ages 6 to 12 years). Based on parameter estimates of the two-trajectory models for each of the four psychological features, a parallel process growth mixture model identified eight significant developmental patterns that were subsequently compared with typically developing children. Furthermore, we observed that while interpersonal callousness conferred an increased risk for childhood and adolescence conduct problems, its co-occurrence with hyperactivity/impulsivity, irritability, and/or depressive–anxiety symptoms heightened the general risk, but also predicted distinct subtypes of conduct problems (i.e., aggressive and rule-breaking behaviors). Thus, by studying complex developmental combinations of psychological features, we observed qualitatively distinct pathways towards conduct problems. A multitrajectory framework of psychological features should be considered as a significant step towards unveiling the multiple etiological pathways leading to conduct disorder and its substantial clinical heterogeneity.

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Re: A Population-Based Nested Case-Control Study: The Use of 5-Alpha-Reductase Inhibitors and the Increased Risk of Osteoporosis Diagnosis in Patients with Benign Prostate Hyperplasia

The Journal of Urology ◽

10.1016/j.juro.2016.06.043 ◽

2016 ◽

Vol 196 (3) ◽

pp. 848-851

Author(s):

Steven A. Kaplan

Keyword(s):

Case Control Study ◽

Benign Prostate Hyperplasia ◽

Population Based ◽

Prostate Hyperplasia ◽

Reductase Inhibitors ◽

Increased Risk ◽

Nested Case Control ◽

Benign Prostate ◽

5 Alpha Reductase Inhibitors ◽

Control Study

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Erratum

PEDIATRICS ◽

10.1542/peds.84.4.612 ◽

1989 ◽

Vol 84 (4) ◽

pp. 612-612

Keyword(s):

Ultraviolet Light ◽

Skin Color ◽

Social Norm ◽

Sun Exposure ◽

Sun Protection ◽

Social Perceptions ◽

Increased Risk ◽

Ineffective Efforts ◽

Per Se

In the commentary, "Sunburns, Melanoma, and the Pediatrician," by Williams and Sagebiel (Pediatrics 1989;84:381-382), three lines were omitted from the bottom of p 381. The whole paragraph is reprinted here. It is clear that a change is required in social perceptions in which a suntan is equated with health and beauty—not because suntans per se are unhealthy (the deleterious effects of ultraviolet light at suberythemogenic levels are not wellestablished), but because the persistent and often futile efforts of those who constitutionally have less pigment to achieve a tan have serious long-term health consequences. Ideally, there should be a social norm of beauty in which the natural differences in skin color are appreciated and black, tan, pink, and all shades in between are celebrated. Similarly, we need to change our thinking about freckles and solar lentigines. These are not "cute" but represent the ineffective efforts of melanocytes in genetically underpigmented skin to provide protective pigmentation in response to solar stress. Although pediatricians alone cannot change social concepts of beauty, we can instruct our patients and their families about sun protection and we can monitor them for early signs of excessive sun exposure. Weinstock et al demonstrated an increased risk of melanoma for those who had blistering sunburns in adolescence. Although they did not address the risk associated with sunburning prior to ages 15 years, it seems likely that these data can be applied to children of all ages. Therefore, instruction and sun protection should begin in infancy. Moreover, teenagers are known to be both highly conditioned by peer concepts of beauty and relatively impervious to the counsel of their elders. It is essential, therefore, that they enter these years with skin that has been well protected and with minds well indoctrinated.

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