Journal of Neurology

, Volume 259, Issue 10, pp 2161–2166 | Cite as

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
Original Communication


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.


Myotonic dystrophy Comorbidity Neoplasms Risk factors Repeat expansion size 



This study was supported in-part by the Intramural Research Program of the National Cancer Institute, USA, and the University of Rochester’s Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (NIH/U54/NS048843), the National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members (NIH/N01-AR-50-227450), and the National Center for Research Resources and the National Center for Advancing Translational Sciences (NIH: UL1 RR024160). Dr. Das is supported by the Preventive Medicine Residency Program, University of Maryland School of Medicine.

Conflicts of interest


Supplementary material

415_2012_6476_MOESM1_ESM.doc (71 kb)
Supplementary material 1 (DOC 71 kb)


  1. 1.
    Harper PS (2001) Myotonic dystrophy. WB Saunders, PhiladelphiaGoogle Scholar
  2. 2.
    Ranum LP, Day JW (2002) Myotonic dystrophy: clinical and molecular parallels between myotonic dystrophy type 1 and type 2. Curr Neurol Neurosci Rep 2:465–470PubMedCrossRefGoogle Scholar
  3. 3.
    Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 69:385PubMedGoogle Scholar
  4. 4.
    Fu YH, Pizzuti A, Fenwick RG Jr, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong D (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255:1256–1258PubMedCrossRefGoogle Scholar
  5. 5.
    Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barcelo J, O’Hoy K (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255:1253–1255PubMedCrossRefGoogle Scholar
  6. 6.
    Liquori CL, Ricker K, Moseley ML, Jacobsen JF, Kress W, Naylor SL, Day JW, Ranum LP (2001) Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 293:864–867PubMedCrossRefGoogle Scholar
  7. 7.
    Mueller CM, Hilbert JE, Martens W, Thornton CA, Moxley RT, III, Greene MH (2009) Hypothesis: neoplasms in myotonic dystrophy. Cancer Causes Control 20(10):2009–2020Google Scholar
  8. 8.
    Gadalla SM, Lund M, Pfeiffer RM, Gortz S, Mueller CM, Moxley RT III, Kristinsson SY, Bjorkholm M, Shebl FM, Hilbert JE, Landgren O, Wohlfahrt J, Melbye M, Greene MH (2011) Cancer risk among patients with myotonic muscular dystrophy. JAMA 306:2480–2486PubMedCrossRefGoogle Scholar
  9. 9.
    Win AK, Perattur PG, Pulido JS, Pulido CM, Lindor NM (2012) Increased cancer risks in myotonic dystrophy. Mayo Clin Proc 87(2):130–135PubMedCrossRefGoogle Scholar
  10. 10.
    Hilbert JE, Kissel JT, Luebbe EA, Martens WB, McDermott MP, Sanders DB, Tawil R, Thornton CA, Moxley RT III (2012) If you build a rare disease registry, will they enroll and will they use it? Methods and data from the National Registry of Myotonic Dystrophy (DM) and Facioscapulohumeral Muscular Dystrophy (FSHD). Contemp Clin Trials 33:302–311PubMedCrossRefGoogle Scholar
  11. 11.
    Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR (2004) A census of human cancer genes. Nat Rev Cancer 4:177–183PubMedCrossRefGoogle Scholar
  12. 12.
    Lahiry P, Torkamani A, Schork NJ, Hegele RA (2010) Kinase mutations in human disease: interpreting genotype-phenotype relationships. Nat Rev Genet 11:60–74PubMedCrossRefGoogle Scholar
  13. 13.
    Miller RW, Rubinstein JH (1995) Tumors in Rubinstein–Taybi syndrome. Am J Med Genet 56:112–115PubMedCrossRefGoogle Scholar
  14. 14.
    Pujol RM, Casanova JM, Egido R, Pujol J, de Moragas JM (1995) Multiple familial pilomatricomas: a cutaneous marker for Gardner syndrome? Pediatr Dermatol 12:331–335PubMedCrossRefGoogle Scholar
  15. 15.
    Azurdia RM, Verbov JL (1999) Myotonic dystrophy and basal cell carcinoma—a true association? Br J Dermatol 141:941–942PubMedCrossRefGoogle Scholar
  16. 16.
    Goolamali SI, Edmonds EV, Francis N, Bunker CB (2009) Myotonic dystrophy and basal cell carcinomas: coincidence or true association? Clin Exp Dermatol 34:e370PubMedCrossRefGoogle Scholar
  17. 17.
    Itin PH, Laeng RH (2001) Multiple pigmented basalioma of the scalp in a patient with Curschmann-Steinert myotonia dystrophica. Confirmation of a rare symptom constellation. Hautarzt 52:244–246PubMedCrossRefGoogle Scholar
  18. 18.
    Zemtsov A (2010) Association between basal, squamous cell carcinomas, dysplastic nevi and myotonic muscular dystrophy indicates an important role of RNA-binding proteins in development of human skin cancer. Arch Dermatol Res 302:169–170PubMedCrossRefGoogle Scholar
  19. 19.
    Panzer S, Kuhl DP, Caskey CT (1995) Unstable triplet repeat sequences: a source of cancer mutations? Stem Cells 13:146–157PubMedCrossRefGoogle Scholar
  20. 20.
    Groh WJ, Groh MR, Shen C, Monckton DG, Bodkin CL, Pascuzzi RM (2011) Survival and CTG repeat expansion in adults with myotonic dystrophy type 1. Muscle Nerve 43:648–651PubMedCrossRefGoogle Scholar
  21. 21.
    Schoser BG, Kress W, Walter MC, Halliger-Keller B, Lochmuller H, Ricker K (2004) Homozygosity for CCTG mutation in myotonic dystrophy type 2. Brain 127:1868–1877PubMedCrossRefGoogle Scholar
  22. 22.
    Akiyama M, Yuza Y, Yokokawa Y, Yokoi K, Ariga M, Eto Y (2008) Differences in CTG triplet repeat expansion in leukemic cells and normal lymphocytes from a 14-year-old female with congenital myotonic dystrophy. Pediatr Blood Cancer 51:563–565PubMedCrossRefGoogle Scholar
  23. 23.
    Jinnai K, Sugio T, Mitani M, Hashimoto K, Takahashi K (1999) Elongation of (CTG)n repeats in myotonic dystrophy protein kinase gene in tumors associated with myotonic dystrophy patients. Muscle Nerve 22:1271–1274PubMedCrossRefGoogle Scholar
  24. 24.
    Osanai R, Kinoshita M, Hirose K, Homma T, Kawabata I (2000) CTG triplet repeat expansion in a laryngeal carcinoma from a patient with myotonic dystrophy. Muscle Nerve 23:804–806PubMedCrossRefGoogle Scholar
  25. 25.
    Jansen G, Willems P, Coerwinkel M, Nillesen W, Smeets H, Vits L, Howeler C, Brunner H, Wieringa B (1994) Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n repeat variation and selection against extreme expansion in sperm. Am J Hum Genet 54:575–585PubMedGoogle Scholar
  26. 26.
    Banuls J, Botella R, Palau F, Ramon R, Diaz C, Paya A, Carnero L, Vergara G (2004) Tissue and tumor mosaicism of the myotonin protein kinase gene trinucleotide repeat in a patient with multiple basal cell carcinomas associated with myotonic dystrophy. J Am Acad Dermatol 50:S1–S3PubMedCrossRefGoogle Scholar
  27. 27.
    Bergmann MM, Calle EE, Mervis CA, Miracle-McMahill HL, Thun MJ, Heath CW (1998) Validity of self-reported cancers in a prospective cohort study in comparison with data from state cancer registries. Am J Epidemiol 147:556–562PubMedCrossRefGoogle Scholar
  28. 28.
    Desai MM, Bruce ML, Desai RA, Druss BG (2001) Validity of self-reported cancer history: a comparison of health interview data and cancer registry records. Am J Epidemiol 153:299–306PubMedCrossRefGoogle Scholar
  29. 29.
    Klein BE, Lee KE, Moss SE, Trentham-Dietz A, Klein R (2010) Self- and registry-reported cancer in a population-based longitudinal study. WMJ 109:261–266PubMedGoogle Scholar

Copyright information

© Springer-Verlag (outside the USA) 2012

Authors and Affiliations

  • Maya Das
    • 1
  • Richard T. Moxley III
    • 2
  • James E. Hilbert
    • 2
  • William B. Martens
    • 2
  • Lisa Letren
    • 1
  • Mark H. Greene
    • 3
  • Shahinaz M. Gadalla
    • 3
    • 4
  1. 1.Department of Epidemiology and Public HealthUniversity of MarylandBaltimoreUSA
  2. 2.Department of Neurology, Neuromuscular Disease CenterUniversity of Rochester Medical CenterRochesterUSA
  3. 3.Clinical Genetics Branch, Division of Cancer Epidemiology and GeneticsNational Cancer Institute, NIHBethesdaUSA
  4. 4.Clinical Genetics Branch, Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleUSA

Personalised recommendations