Risk of cancer among Finnish multiple sclerosis patients

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: BC, breast cancer; BMI, body mass index; Breast cancer; CI, confidence interval; CNS, central nervous system; Cohort study; DMF, dimethyl fumarate; DMT; DMT, disease modifying treatment; EBV, Epstein-Barr virus; GA, glatiramer acetate; Glossary: MS, multiple sclerosis; HL, Hodgkin lymphoma; ICD, International Classification of Diseases; IFN, interferon; IS, immunosuppressant; MRI, magnetic resonance image; Multiple sclerosis; OR, odds ratio; PPMS, primary progressive MS; RRMS, relapsing remitting MS; SPMS, secondary progressive MS; TFR, teriflunomide.