Correlates of tumor development in patients with myotonic dystrophy

Maya Das, Richard T. Moxley III, James E. Hilbert, William B. Martens, Lisa Letren, Mark H. Greene, Shahinaz M. Gadalla

Patients with myotonic dystrophy (DM) have recently been reported to be at increased risk of tumor development, but clinical associations related to this observation are unknown. We calculated the odds ratios (ORs) and 95 % confidence intervals (CI) of self-reported tumor development by patients' demographic and clinical characteristics to evaluate factors associated with tumor development in DM patients, using data from the National Registry of Myotonic Dystrophy and Facioscapulohumeral Dystrophy Patients and Family Members. Of the 911 participants, 47.5 % were male and 85.7 % had DM type 1 (DM1). Compared to DM1, patients with DM type 2 (DM2) were older at registry enrollment (median age 55 vs. 44 years, p < 0.0001) and at DM diagnosis (median age 48 vs. 30 years, p < 0.0001); and more likely to be females (p = 0.001). At enrollment, 95 (10.4 %) DM patients reported a history of benign or malignant tumor. Tumors were associated with female gender (OR 1.9, 95 % CI 1.2-3.1, p = 0.007) and DM1 (OR 2.1, 95 % CI 1.1-4.1, p = 0.03). In a subgroup analysis of patients with blood-based DNA testing results (397 DM1, 54 DM2), repeat expansion size was not associated with tumor risk in DM1 (p = 0.26) or DM2 (p = 0.34). In conclusion, female gender and DM1 subtype, but not DNA repeat expansion size, were associated with increased risk of tumors in DM. Follow-up studies are warranted to determine if oncogenes associated with dystrophia myotonica-protein kinase are altered in DM, and to determine if repeat expansion size, as in our study, is not associated with tumor development.