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Multiple sclerosis and risk of cancer: a meta-analysis
  1. Adam E Handel1,2,
  2. Sreeram V Ramagopalan1,2
  1. 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  2. 2Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, UK
  1. Correspondence to Dr Sreeram V Ramagopalan, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; sreeramr{at}

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We read with interest the study by Fois and colleagues, showing no change in the risk of cancer in multiple sclerosis (MS) patients compared with the normal population.1 However, we note that a previous study published this year suggested that MS patients are at lower risk of cancer than the normal population.2 Resolving this controversy is of huge importance for patients and perhaps also for assessing potential adverse effects of immunomodulatory therapies for MS.3

These recent reports, utilising powerful population-based registries, have both shown a decreased risk for all cancers in MS patients, with statistical significance achieved in one study2 but not in the other.1 As the conclusions drawn from these studies were conflicting, there is potential for confusion in the field as to whether or not MS patients are actually at a decreased risk of cancer.1 2

Given the similar ORs obtained in both studies, we reasoned that a meta-analysis would provide more information. We investigated all studies published in the last 15 years reporting measures of the risk of cancer for an MS cohort relative to population controls. This yielded a total of five studies: Fois and colleagues from the UK1; Bahmanyar and colleagues from Sweden2; Lebrun and colleagues from France3; Nielsen and colleagues from Denmark4; and Midgard and colleagues from Norway.5 We used the figures presented by Fois and colleagues for cancers diagnosed after presentation with MS. Using the generic inverse variance with random effects model in Review Manager 5.0, we calculated the overall OR for all cancers combined.

By pooling these studies, data were available on 45 032 MS patients. There was no significant heterogeneity between studies (p=0.16). We found that there was a significantly decreased risk of all cancers (see figure 1) in the MS cohort relative to controls (OR 0.92 (95% CI 0.87 to 0.97) p=0.004).

Figure 1

Forest plot of the risk of cancer in multiple sclerosis. This forest plot shows the ORs and 95% CIs for the multiple sclerosis cohort relative to the control cohort in each individual study and the pooled results for all cancers. The model used was generic inverse variance (IV) and random effects.

Our findings therefore lend support to the concept of a small but significant decrease in cancer risk for patients with MS but cannot define how this disabling neurological condition affects cancer risk. Although it could be argued that this reduction may simply be the result of reduced life expectancy in MS patients, this is unlikely, as an age-specific Cox survival model also showed a significant reduction in the risk of cancer.2 Similarly, it is unlikely that this would represent under-reporting of cancer because patients are typically in closer contact with health practitioners than the normal population.2 Explanations could include lifestyle alterations following diagnosis, genetic factors or immunological changes due to MS. Further study of mechanisms is therefore warranted, but more immediately, the results of this meta-analysis will be of use for MS patients and their care givers.


We would like to thank all members of the Ebers group for helpful discussion and frequent support.


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  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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