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Risk of cancer among Finnish multiple sclerosis patients

Published:August 05, 2019DOI:https://doi.org/10.1016/j.msard.2019.08.005

      Highlights

      • Overall cancer risk was equal among MS patients and controls in our study cohort.
      • Age at breast cancer diagnosis was significantly higher among MS patients.
      • Breast cancer risk was non-significantly lower among MS patients compared to controls.
      • Impact of MS therapeutics or smoking on the risk of cancer could not be evaluated.

      Abstract

      Background

      Most studies that have investigated the association between multiple sclerosis (MS) and cancer have suggested a reduced overall cancer risk and no effect of long-term exposure to the immunomodulatory disease modifying treatments (DMTs). Some studies have suggested an increased cancer risk among MS patients treated with immunosuppressive (IS) therapies. Cancer risk among Finnish MS patients has previously been studied from an incidence cohort from 1964 to 1993 followed until year 1999. The objective of this nested case-control study was to assess the cancer risk among Finnish MS patients in a hospital district cohort from southwest Finland during the DMT era.

      Methods

      Patients with MS and cancer comorbidity were identified from the hospital administrative data at the Hospital District of Southwest Finland during a period from 1.1.2004 to 31.12.2012. Case ascertainment for MS diagnosis by the McDonald criteria was performed by review of medical records. During the follow-up 1074 confirmed MS cases were treated in the hospital district, including the deceased cases after 1.1.2004 (5.9%, n = 70). The randomly chosen 10-fold control population was matched by birth year and gender to calculate the coincident risks (odds ratio, OR) with 95% confidence intervals (95% CI) for each cancer diagnosis. Another separate control population from the same patient pool was used to verify the stability of the results. The Kaplan-Meier analysis and ANOVA test log rank test was applied to study cumulative index proportion and age (years) at breast cancer diagnosis in the MS and in the control group.

      Results

      A total of 61 (5,7%) of the MS patients and 757 (7,0%) of the controls were diagnosed with cancer during the study period. The overall risk of cancer in the MS cohort did not significantly differ form the controls (OR 0.80, 95% CI 0.6–1.0, p = 0.092). The age at breast cancer diagnosis in the MS cohort was statistically significantly higher in comparison to the control cohort (61,7 vs. 55.7 years, ANOVA test p-value 0.010). However, the risk for breast cancer did not statistically significantly differ between MS patients and controls (OR 0.9, 95% CI 0.5–1.4, p-value 0.566). In the MS cohort we observed an increased risk of oral cavity cancers (OR 10, CI 1.1–94.2, p-value 0.04), colon cancer (OR 2.3, 95% CI 1.1–5.2, p-value 0.037), lung cancer (OR 4.4, CI 1.5–13.0, p-value 0.007), renal cancer (OR 3.6, CI 1.2–10.6, p-value 0.018), brain cancer (OR 5, 95% CI 1.1–23.0, p-value 0.039) and thyroid cancer (OR 3.6, 95% CI 1.2–10.6, p-value 0.018), and a decreased risk for prostate cancer (OR 0.2, 95% CI 0.1–0.8, p-value 0.026), although for these cancer subtypes the patient numbers were small.

      Conclusions

      Overall risk of cancer in our MS cohort did not significantly differ from the controls. However, the age at diagnosis of breast cancer was statistically significantly higher among the MS patients in comparison with a control population from the same patient pool. Further population-based larger studies spanning longer follow-up periods and longer exposure to emerging MS therapies are needed to evaluate cancer risk related to MS treatments and breast cancer risk in particular.

      Keywords

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      References

        • Achiron A.
        • et al.
        Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments.
        Breast Cancer Res. Treat. 2005; 89 (2005 FebPMID:15754125): 265-270https://doi.org/10.1007/s10549-004-2229-4
        • Ajdadic-Gross V.
        • et al.
        Cancer co-occurrence patterns in Parkinsons disease and multiple sclerosis – Do they mirror immune system imbalances?.
        Cancer Epidemiol. 2016; 44 (2016 OctEpub 2016 Sep 6. PMID:27612279): 167-173https://doi.org/10.1016/j.canep.2016.08.018
        • Anagnostouli M.
        • et al.
        HLA-DRB1*15:01 and Epstein-Barr virus in a multiple sclerosis patient with psoriasis, nasopharyngeal and breast cancers. Lessons for possible hidden links for autoimmunity and cancer.
        J. Neurol. Sci. 2014; 339 (2014 Apr 15Epub 2014 Feb 11): 26-31https://doi.org/10.1016/j.jns.2014.02.003
        • Bar-Or A.
        The immunology of multiple sclerosis.
        Semin. Neurol. 2008; 28 (2008 FebReview. PMID:18256985): 29-45https://doi.org/10.1055/2-2007-1019124
        • Boussios S.
        • et al.
        2015 Neuroendocrine cell carcinoma of unknown primary arising in long-standing history of multiple sclerosis.
        Case Rep. Oncol. Med. 2015; 2015 (Epub 2015 Mar 24)135976https://doi.org/10.1155/2015/135976
        • Capkun G.
        • et al.
        Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: an observational study using the US department of defense administrative claims database.
        Mult. Scler. Relat. Disord. 2015; 4 (2015 NovEpub 2015 Aug 18. PMID:26590661): 546-554https://doi.org/10.1016/j.msard.2015.08.005
        • Clerico M.
        • et al.
        Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis.
        Expert Opin. Drug Saf. 2017; 16 (2017 AugEpub 2017 Jul 5. PMID:28641055): 963-972https://doi.org/10.1080/14740338.2017.2346082
        • Coles A.J.
        • et al.
        Alemtuzumab CARE-MS II 5-year follow-up: efficacy and safety findings.
        Neurology. 2017; 89 (2017 Sep 12Epub 2017 Aug 23. PMID28835403): 1117-1126https://doi.org/10.1212/WNL.0000000000004354
        • Comi G.
        • et al.
        Benefit-risk profile of sphingosine-1-phosphate receptor modulators in relapsing and secondary progressive multiple sclerosis.
        Drugs. 2017; 77 (2017 OctReview): 1755-1768https://doi.org/10.1007/s40265-017-0814-1
        • D´Amico E.
        Comparable efficacy and safety of dimethyl fumarate and teriflunomide treatment in relapsing-remitting multiple sclerosis: an Italian real-world multicenter experience.
        Ther. Adv. Neurol. Disord. 2018; 11 (2018 Sep 10eCollection 2018. PMID:30210582)1756286404https://doi.org/10.1177/1756286418796404
        • Ellis R.
        • et al.
        Therapy-related acute leukaemia with mitoxantrone: four years on, what is the risk and can it be limited?.
        Mult. Scler. 2015; 21 (2015 AprEpub 2014 Jul 10. Review): 642-645https://doi.org/10.1177/1352458514541508
        • Friend K.B.
        • et al.
        Smoking rates and smoking cessation among individuals with multiple sclerosis.
        Disabil. Rehabil. 2006; 28 (2006 Sep 30PMID:16966234): 1135-1141https://doi.org/10.1080/09638280500533707
        • Gaindh D.
        • et al.
        Decreased risk of cancer in multiple sclerosis patients and analysis of the effect of disease modifying therapies on cancer risk.
        J. Neurol. Sci. 2016; 370 (2016 Nov 15Epub 2016 Sep 9): 13-17https://doi.org/10.1016/j.jns.2016.09.005
        • Giovannoni G.
        Cladribine to treat relapsing forms of multiple sclerosis.
        Neurotherapeutics. 2017; 14 (2017 OctReview. PMID:29168160): 874-887https://doi.org/10.1007/s13311-017-0573-4
        • Hajiebrahimi M.
        • et al.
        Risk of premenopausal and postmenopausal breast cancer among multiple sclerosis patients.
        PLoS One. 2016; 11 (2016 Oct 24eCollection 2016. PMID: 27776164. PMCID:PMC5077134)e0165027https://doi.org/10.1371/journal.pone.0165027
        • Hauser S.L.
        • et al.
        Ocrelizumab versus interferon beta-1a in relapsing-remitting multiple sclerosis.
        N. Eng. J. Med. 2017; 376 (2017 Jan 19Epub 2016 Dec 21. PMID:28002679): 221-234https://doi.org/10.1056/NEJMoa1601277
        • Havrdova
        • et al.
        Understanding the positive benefit: risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the alemtuzumab clinical development program.
        Ther. Clin. Risk Manag. 2017; 13 (2017 Oct 16eCollection 2017. Review. PMID:29081658): 1423-1437https://doi.org/10.2147/TCRM.S143509
        • Hedström A.K.
        • et al.
        Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis.
        Neurology. 2009; 73 (2009 Sep 1PMID:1972): 696-701https://doi.org/10.1212/WNL.0b013e3181b59c40
        • Hedström A.K.
        • et al.
        Smoking is a major preventable risk factor for multiple sclerosis.
        Mult. Scler. 2015; 22 (2016 JulEpub 2015 Oct 12. PMID:26459151): 1021-1026https://doi.org/10.1177/1352458515609794
        • Holmberg M.
        • et al.
        Increased female MS incidence and differences in gender-specific risk in medium- and high-risk regions in Finland from 1981 to 2010.
        Mult. Scler. Int. 2013; 2013 (2013Epub 2013 Nov 10. Review. PMID:24324888)182516https://doi.org/10.1155/2013/182516
        • Holzmann C.
        • et al.
        Co-occurrence of multiple sclerosis in a BRCA1 positive family.
        Eur. J. Med. Genet. 2013; 56 (2013 OctEPub 2013 Aug 14. PMID:23954390): 577-579https://doi.org/10.1016/j.ejmg.2013.07.006
        • Huang O.
        • et al.
        Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells.
        Exp. Biol. Med. (Maywood). 2015; 240 (2015 Apr10.1177.1535370214554881. Epub 2014 Oct 10. PMID:25304315): 426-437
        • Jiang L.
        • et al.
        Anti-inflammatory drug, leflunomide and its metabolite teriflunomide inhibit NSCLC proliferation in vivo and in vitro.
        Toxicol. Lett. 2018; 282 (2018 Jan 5Epub 2017 Oct 16. PMID29050931): 154-165https://doi.org/10.1016/j.toxlet.2017.10.013
        • Khankanian P.
        • et al.
        Meta-analysis of genome-wide association studies reveals genetic overlap between Hodgkin lymphoma and multiple sclerosis.
        Int. J. Epidemiol. 2016; (2016 Mar 12Pii: dyv364 [Epub ahead of print])
        • Kingwell E.
        • et al.
        Cancer risk in multiple sclerosis: findings from British Columbia, Canada.
        Brain. 2012; 2012: 2973-2979https://doi.org/10.1093/brain/aws148
        • Kingwell E.
        • et al.
        Assessment of cancer risk with β-interferon treatment for multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 2014; 85 (2014 OctEpub 2014 Mar 4): 1096-1102https://doi.org/10.1136/jnnp-2013-307238
        • Krhut J.
        • et al.
        Incidence of the urological tumors in patients suffering from multiple sclerosis.
        Acta Neurol. Scand. 2014; 130 (2014 SepEpub 2014 May 8): 193-196https://doi.org/10.1111/ane.12264
        • Krökki O.
        • et al.
        Increasing incidence of multiple sclerosis in women in northern Finland.
        Mult. Scler. 2011; 17 (2011 FeEpub 2010 Oct 8. PMID:20935028): 133-138https://doi.org/10.1177/1352458510384012
        • Kyritsis A.P.
        • et al.
        Cancer specific risk in multiple sclerosis patients.
        Crit. Rev. Oncol. Hematol. 2015; 98 (2016 FebEpub 2015 Oct 9): 29-34https://doi.org/10.1016/j.critrevonc.2015.10.002
        • Le Bouc R.
        • et al.
        No increase in cancer incidence detected after cyclophosphamide in a French cohort of patients with progressive multiple sclerosis.
        Mult. Scler. 2012; 18 (2012 JanEpub 2011 Aug 15. PMID:21844065): 55-63https://doi.org/10.1177/1352458511416839
        • Lebrun C.
        • et al.
        Cancer risk and impact of disease modifying treatments in patients with multiple sclerosis.
        Mult. Scler. 2008; 14 (2008 AprPMID:18420778): 399-405https://doi.org/10.1177/1352458507083625
        • Lebrun C.
        • et al.
        Cancer and MS in the era of disease-modifying treatments.
        J. Neurol. 2011; 258 (2011 JulEpub 2011 Feb 4. PMID:21293872): 1304-1311https://doi.org/10.1007/s00415-011-5929-9
        • Lebrun Christine
        • Rocher Fanny
        Cancer risk in patients with multiple sclerosis: potential impact of disease-modifying drugs.
        CNS Drugs. 2018; 32 (2018 OctReview. PMID:30143945): 939-949https://doi.org/10.1007/s40263-018-0564-y
        • Levin L.I.
        • et al.
        Primary infection with the Epstein-Barr virus and risk of multiple sclerosis.
        Ann. Neurol. 2010; 67 (2010 JunPMID): 824-830https://doi.org/10.1002/ana.21978
        • Marrie R.A.
        • et al.
        A systematic review of the incidence and prevalence of cancer in multiple sclerosis.
        Mult. Scler. 2015; 21 (2015 MarEpub 2015 Jan 26. Review. PMID:25623244): 263-281https://doi.org/10.1177/1352458514564491
        • McGinley
        • et al.
        Safety of monoclonal antibodies for the treatment of multiple sclerosis.
        Expert Opin. Drug Saf. 2017; 16 (2017 JanEpub 2016 Oct 31. Review. PMID27756172): 89-100
        • Montalban X.
        • et al.
        Ocrelizumab versus placebo in primary progressive multiple sclerosis.
        N. Engl. J. Med. 2017; 376 (2017 Jan 19Epub 2016 Dec 21. PMID28002688): 209-220https://doi.org/10.1056/NEJMoa1606468
        • Moroni L.
        • et al.
        Geoepidemiology, gender and autoimmune disease.
        Autoimmun. Rev. 2012; 11 (2012 MayEpub 2011 Nov 28. Review. PMID:22142547): A386-A392https://doi.org/10.1016/j.autorev.2011.11.012
        • Murtonen A.
        • et al.
        Common comorbidities and survival in MS: risk for stroke, type 1 diabetes and infections.
        Mult. Scler. Relat. Disord. 2018; 19 (2018 JanEpub 2017 Nov 13. PMID:29190573): 109-114https://doi.org/10.1016/j.msard.2017.10.019
        • Nortvedt M.W.
        • et al.
        Multiple sclerosis and lifestyle factors: the Hordaland health study.
        Neurol. Sci. 2005; 26 (2005 DecPMID:16388368): 334-339https://doi.org/10.1007/s10072-005-0498-2
        • Nørgaard
        • et al.
        Multiple sclerosis and cancer incidence: a Danish nationwide cohort study.
        Mult. Scler. Relat. Disord. 2018; 28 (2019 FebEpub 2018 Dec 14. PMID:30576846): 81-85https://doi.org/10.1016/j.msard.2018.12.014
        • O´Malley P.W.
        • et al.
        Multiple sclerosis and breast cancer.
        J. Neurol. Sci. 2015; 356 (2015 Sep 15Epub 2015 Jun 22. PMID:26130448): 137-141https://doi.org/10.1016/j.jns.2015.06.033
        • Pirttisalo A.L.
        • et al.
        Multiple sclerosis epidemiology in Finland: regional differences and high incidence.
        Acta Neurol. Scand. 2018; (2018 Nov 27[Epub ahead of print] PMID:30480315)https://doi.org/10.1111/ane.13057
        • Pirttisalo A.L.
        • et al.
        Adult hospital admissions associated with multiple sclerosis in Finland in 2004-2014.
        Ann. Med. 2018; 50 (2018 JunEpub 2018 Apr 17. PMID:29629575): 354-360https://doi.org/10.1080/07853890.2018.1461919
      1. Eero Pukkala and Matti Rautalahti, 2013. Cancer in Finland. Publications from the Cancer Society of Finland 2013. ISBN 978-952-5815-16-0, ISBN 978-952-5815-17-7 (pdf). Cancer Society of Finland Publication No. 86, p. 26–29.

        • Ragonese
        • et al.
        Association between multiple sclerosis, cancer risk and immunosuppressant treatment: a cohort study.
        BMC Neurol. 2017; 17 (2017 Aug 8PMID:29132407): 155https://doi.org/10.1186/s12883-017-0932-0
        • Ramanujam R.
        • et al.
        Effect of smoking cessation on multiple sclerosis prognosis.
        JAMA Neurol. 2015; 72 (2015 OctPMID26348720): 1117-1123https://doi.org/10.1001/jamaneurol.2015.1788
        • Rosati G.
        The prevalence of multiple sclerosis in the world: an update.
        Neurol. Sci. 2001; 22 (2001 AprReview. PMID:11603614): 117-139
        • Roshanisefat H.
        • et al.
        All-cause mortality following a cancer diagnosis amongst multiple sclerosis patients: a Swedish population based cohort study.
        Eur. J. Neurol. 2015; 22 (2015 JulEpub 2015 Apr 22): 1074-1080https://doi.org/10.1111/ene.12710
        • Sabol R.A.
        • et al.
        Melanoma complicating treatment with natalizumab for multiple sclerosis: a report from the southern network on adverse reactions (SONAR).
        Cancer Med. 2017; 6 (2017 JulEpub 2017 Jun 20. Review. PPMID: 28635055): 1541-1551https://doi.org/10.1002/cam4.1098
        • Sarasoja T.
        • et al.
        Occurrence of multiple sclerosis in central Finland: a regional and temporal comparison during 30 years.
        Acta Neurol. Scand. 2004; 110 (2004 Nov): 331-336
        • Sumelahti M.L.
        • et al.
        Increasing prevalence of multiple sclerosis in Finland.
        Acta Neurol. Scand. 2001; 103 (2001 MarPMID:11240562): 153-158
        • Sumelahti M.L.
        • et al.
        Multiple sclerosis in Finland: incidence and differences in relapsing remitting and primary progressive disease courses.
        J. Neurol. Neurosurg. Psychiatry. 2003; 74 (2003 JanPMID12486261): 25-28
        • Sumelahti M.L.
        • et al.
        Cancer incidence in multiple sclerosis: a 35-year follow-up.
        Neuroepidemiology. 2004; 23 (2004 Sep-OctPMID:15316248): 224-227https://doi.org/10.1159/000079947
        • Sun L.M.
        • et al.
        Increased breast cancer risk for patients with multiple sclerosis: a nationwide population-based cohort study.
        Eur. J. Neurol. 2014; 21 (2014 Feb12267. Epub 2013 Sep 19): 238-244https://doi.org/10.1111/ene
        • Tabarés-Seisdedos Rafael
        • Rubenstein John L.
        Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders.
        Nat. Rev. Neurosci. 2013; 14 (2013 AprReview. PMID:23511909): 293-304https://doi.org/10.1038/nrn3464
      2. THL Tobacco statistics2017: Health behaviour among the Finnish adult population (AVTK). THL (years 1996-2012). Regional Health and Well-being Study (ATH) (from 2013 onwards). (THL). Health Behaviour and Health among the Finnish Retirement –Age Population (EVTK), THL (years 1997-2011). Regional Health and Well-being Study (ATH) (from 2012 onwards). (THL).

        • Thormann A.
        • et al.
        Inverse comorbidity in multiple sclerosis: findings in a complete nationwide cohort.
        Mult. Scler. Relat. Disord. 2016; 10 (2016 NovEpub 2016 Oct 29. PMID:27919487): 181-186https://doi.org/10.1016/j.msard.2016.10.008
        • Tully T.
        • et al.
        Kaposi sarcoma in a patient with relapsing-remitting multiple sclerosis receiving fingolimod.
        Neurology. 2015; 84 (2015 May 12Epub 2015 Apr 15. PMID25878178): 1999-2001https://doi.org/10.1212/WNL.0000000000001556
        • Turner A.P.
        • et al.
        Smoking among veterans with multiple sclerosis: prevalence correlates, quit attempts, and unmet need for services.
        Arch. Phys. Med. Rehabil. 2007; 88 (2007 NovPMID17964878): 1394-1399
      3. www.cancerregistry.fi, the Finnish cancer registry.

      4. Åivo J. et al. Risk of osteoporotic fractures in multiple sclerosis patients in southwest Finland. Acta Neurol. Scand.. 2017 May; 135(5): 516–521. doi: 10.111/ane.12623. Epub 2016 Jun 22. PMID:27334254.