Autoimmune diseases and risk of glioma

Date of ISAC Approval: 
Lay Summary: 
Autoimmune diseases (AD) such as rheumatoid arthritis and psoriasis arise when one's immune system attacks one's own healthy body cells and tissues. The immune system also plays a role in the development of common brain tumors, the so-called gliomas. Several studies have investigated whether patients with AD have an altered risk of glioma, but the results have been inconclusive thus far. To further the existing evidence, we propose to conduct a study using the U.K.-based Clinical Practice Research Datalink (CPRD) to evaluate the risk of glioma in patients with AD compared to patients without AD. Cases will be individuals with a first ever diagnosis of glioma between 1995 and 2015.
Technical Summary: 
Using data from the CPRD, we intend to perform a 1:10 matched case-control analysis to explore the association between AD and risk of glioma. AD exposure will be defined as the presence of any autoimmune disease at some time one or more years before the diagnosis date of the glioma. Controls will be matched to cases on age, sex, calendar time, general practice, and number of years of active history in the CPRD prior to the index date. Relative risks will be estimated by conducting conditional logistic regression analyses to determine odds ratios (ORs) with 95% confidence intervals (CIs) of glioma in relation to AD. Analyses will be adjusted for potential confounders and only factors altering the risk of glioma by >10% will be included in the final multivariate analysis.
Health Outcomes to be Measured: 
The exposure of interest in this study will be Autoimmune Disease (AD). We will assess AD according to the following list of diseases in Harrison's Principles of Internal Medicine, which includes coding for Graves' disease, Hashimoto thyroiditis, autoimmune polyglandular syndrome, type 1 diabetes mellitus, insulin-resistant diabetes mellitus, Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmne alopecia, vitiligo, autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura, pernicious anaemia, myasthenia gravis, multiple sclerosis, Guillan-Barre syndrome, Stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic lupus erythematosus, rheumatoid arthritis, systemic necrotizing vasculitis, Wegener's granulomatosis, antiphospholipid syndrome, Sjogren's syndrome and additionally Crohn's disease, ulcerative colitis, psoriasis, sarcoidosis, systemic sclerosis, primary biliary cirrhosis, chronic rheumatic heart disease, discoid lupus erythematosus, localised scleroderma, ankylosing spondylitis, haemorrhagic proctitis, polymyalgia rheumatica, Reiter's disease, Dupytren's disease, amyotrophic lateral sclerosis, and induratio penis plastica and celiac disease. A patient will be considered to have an AD if they have any code for one of the diseases listed above at least 1 year prior to the first glioma diagnosis.

Christoph Meier - Chief Investigator - University of Basel
Dr Corinna Seliger - Researcher - University of Regensburg
Dr Katharina Sahm - Collaborator - University of Heidelberg
Professor Michael Leitzmann - Researcher - University of Regensburg
Professor Michael Platten - Collaborator - University of Heidelberg
Professor Peter Hau - Researcher - University of Regensburg
Professor Ralf Linker - Collaborator - University of Regensburg
Dr Susan S Jick - Researcher - BCDSP - Boston Collaborative Drug Surveillance Program