title: Risk of cancer of unknown primary after hospitalization for autoimmune diseases.
abstract: Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964-2012; 2,658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long-time users of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long-term follow-up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP-related immune dysfunction. However, long-term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side effect.
authors.affiliation: Department of Clinical Science in Malmö, Center for Primary Health Care Research, Lund University, Sweden.|Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: Department of Clinical Science in Malmö, Center for Primary Health Care Research, Lund University, Sweden.|Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundquist
authors.affiliation: Department of Clinical Science in Malmö, Center for Primary Health Care Research, Lund University, Sweden.|Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA.
authors.forename: Jan
authors.initials: J
authors.lastname: Sundquist
authors.affiliation: Department of Clinical Science in Malmö, Center for Primary Health Care Research, Lund University, Sweden.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Ji
mesh_terms: D017668:Age of Onset; D001327:Autoimmune Diseases / Q000150:complications* / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D008297:Male; D009382:Neoplasms, Unknown Primary / Q000453:epidemiology / Q000276:immunology*; D012307:Risk Factors
keywords: autoimmune diseases; cancer of unknown primary; national databases