Benign and Malignant Tumors in Patients with Myotonic Dystrophy Type I

Date of ISAC Approval: 
Lay Summary: 
Myotonic Dystrophy (DM) is an inherited disorder primarily affecting muscles. Published case reports suggested that DM patients might be at high risk of various benign (non-cancerous) and malignant (cancerous) tumors. We conducted the first study evaluating cancer risk in DM patients using healthcare data from Sweden and Denmark. Our study found that DM patients had a two-fold increased risk of all cancers combined and excess risk for several site-specific cancers including those of the endometrium (the lining of the uterus), ovary, brain, large bowl, and possibly thyroid gland, pancreas, and skin cancer. In our previous work, we lacked specific data related to DM disease subtype (i.e., type 1 or 2). We also could not assess the risk of DM on benign tumors, since they are not recorded in the Scandinavian cancer registries, and had no data regarding possible factors contributing to this observation. We plan to use anonymised electronic medical records from the CPRD Gold database to quantify tumor burden in DM patients (both benign and malignant), and to identify possible risk factors. This study will inform patient clinical care and may open future avenues for research as we seek to elucidate the causes of tumor development in DM patients.
Technical Summary: 
Myotonic dystrophy (or dystrophia myotonica; DM) is an autosomal dominant multi-system disorder. A previous study of 1,658 DM patients identified from the Swedish and Danish patient registries and linked to the corresponding cancer registries provided the first epidemiological evidence of an elevated cancer risk in DM patients. In this project, we propose to evaluate the risk of both benign and malignant tumors in patients with DM type 1 (DM1, also called Steinert's disease), identify potential clinical factors and risk modifiers for this observation. Accordingly, we plan to compare the risk of developing benign and malignant tumors in a cohort of DM patients identified from CPRD Gold and the integrated hospital episode statistics (HES) database with tumor risk in a matched control cohort of DM1-free individuals. Our analyses will quantify overall and site-specific tumor risks among DM1 patients and will identify risk factors contributing to such events. Analyses will be adjusted for common cancer risk factors (smoking history, BMI, and alcohol use) and for specific risk factors in anatomic site-specific analyses, such as parity in female reproductive cancers.
Health Outcomes to be Measured: 
- Mortality - Benign tumors - Malignant tumors

Dr Shahinaz Gadalla - Chief Investigator - National Cancer Institute (NCI)
Ana Best - Collaborator - National Cancer Institute (NCI)
David Wolfson - Collaborator - McGill University
Hanns Lochmuller - Collaborator - Newcastle University
Ms Julia Gage - Collaborator - National Cancer Institute (NCI)
Dr Lesley Anderson - Collaborator - Queens University Belfast
Dr Mark H Greene - Collaborator - National Cancer Institute (NCI)
Rotana Alsaggaf - Collaborator - National Cancer Institute (NCI)
Ruth Pfeiffer - Collaborator - National Cancer Institute (NCI)
Dr Shahinaz Gadalla - Corresponding Applicant - National Cancer Institute (NCI)
Dr Wilhelmine Meeraus - Collaborator - GlaxoSmithKline - UK
Youjin Wang - Collaborator - National Cancer Institute (NCI)

HES Admitted;ONS;Patient IMD;Practice IMD (Standard)