title: The long-term risk of malignant astrocytic tumors after structural brain injury--a nationwide cohort study.
abstract: BACKGROUND
  Neoplastic transformation of damaged astrocytes has been proposed as a possible pathological mechanism behind malignant astrocytic tumors. This study investigated the association between structural brain injuries causing reactive astrogliosis and long-term risk for malignant astrocytic tumors.
  
  
  METHODS
  The cohort consisted of all individuals living in Denmark between 1978 and 2011. The personal identification number assigned to all individuals allowed retrieval of diagnoses of traumatic brain injury, cerebral ischemic infarction, and intracerebral hemorrhage from the National Patient Discharge Register. Diagnoses of anaplastic astrocytoma and glioblastoma multiforme (World Health Organization grades III and IV) were retrieved from the Danish Cancer Registry. Rate ratios (RR's) were estimated using log-linear Poisson regression.
  
  
  RESULTS
  In a cohort of 8.2 million individuals, 404 812 experienced a structural brain injury and 6152 developed a malignant astrocytic tumor. No significant association was observed 1-4 years after a structural brain injury (RR = 1.14; 95% CI: 0.87-1.46), whereas the long-term (5+ y) risk for malignant astrocytic tumors was significantly reduced (RR = 0.68; 95% CI: 0.49-0.90) compared with no injury. The specific long-term risks by type of injury were: traumatic brain injury RR = 0.32 (95% CI: 0.10-0.75); cerebral ischemic infarction RR = 0.69 (95% CI: 0.47-0.96); and intracerebral hemorrhage RR = 1.39 (95% CI: 0.64-2.60).
  
  
  CONCLUSIONS
  We found no evidence for an association between structural brain injury and malignant astrocytic tumors within the first 5 years of follow-up. However, our study indicated a protective effect of astrogliosis-causing injuries 5 or more years after structural brain injury.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (T.N.M., S.G., J.W., M.M.); Department of Neurosurgery, Copenhagen University Hospital, Denmark (T.N.M.).
authors.forename: Tina Noergaard
authors.initials: TN
authors.lastname: Munch
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (T.N.M., S.G., J.W., M.M.); Department of Neurosurgery, Copenhagen University Hospital, Denmark (T.N.M.).
authors.forename: Sanne
authors.initials: S
authors.lastname: Gørtz
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (T.N.M., S.G., J.W., M.M.); Department of Neurosurgery, Copenhagen University Hospital, Denmark (T.N.M.).
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (T.N.M., S.G., J.W., M.M.); Department of Neurosurgery, Copenhagen University Hospital, Denmark (T.N.M.).
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000453:epidemiology / Q000209:etiology*; D001930:Brain Injuries / Q000150:complications* / Q000453:epidemiology; D001932:Brain Neoplasms / Q000453:epidemiology / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005909:Glioblastoma / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
keywords: anaplastic astrocytoma; astrogliosis; brain injury; epidemiology; glioblastoma