title: Histological concordance in familial central nervous system tumors: Evidence from nationwide Swedish Family-Cancer Database.
abstract: BACKGROUND
  Published studies have shown that familial risks in the primary central nervous system (CNS) tumors are usually histology-specific. If genetic factors indeed determine tumor histology it would be expected that histological types would agree between affected first-degree relatives (FDRs).
  
  
  METHODS
  This study was conducted using the nationwide Swedish Family-Cancer Database. FDR pairs were defined where both of them had the same histological subtype of CNS tumor. The histological concordance was determined using kappa agreement test.
  
  
  RESULTS
  We identified 858 familial patients (333 parent-offspring pairs, 97 sibling pairs) with primary CNS tumors. Proportion of spinal hemangioblastoma out of all familial hemangioblastomas (21%) was significantly higher than that in sporadic patients (7%; P=0.001). The highest kappa value was found for hemangioblastoma among parent-child pairs (kappa=86%, 95% CI: 74-98%). There was a moderate agreement for concordant neurinoma among father-daughter pairs (kappa=48% 95% CI: 15-81%). Low grade glioma showed significant agreement among mother-daughter (kappa=33%, 95% CI: 9-57%) and father-daughter pairs (kappa=39%, 95% CI: 11-67%), but not in mother-son (kappa=10%, 95% CI: -13% to 32%) and father-son pairs (kappa=9%, 95% CI: -1% to 40%). There was histological agreements for meningioma in mother-offspring (kappa range=20-27%) but not in father-daughter (kappa=14%, 95% CI: -8% to 35%) and father-son pairs (kappa=9%, 95% CI: -12% to 30%).
  
  
  CONCLUSIONS
  Our findings suggest that shared genetic risk factors between family members could lead to specific histological types in the familial CNS tumors, especially in hemangioblastoma and neurinoma. Our data may also suggest interactions between sex hormone and some genes contributing to familial meningioma and low grade glioma.
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany; Ardabil Cancer Registry, Ardabil University of Medical Sciences, Ardabil, Iran. Electronic address: m.babaei@dkfz.de.
authors: M
authors: M
authors: Babaei
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors: M
authors: M
authors: Fallah
authors: Center for Primary Health Care Research, Lund University, Malmö, Sweden; Stanford Prevention Research Center, Stanford University School of Medicine, California, USA.
authors: K
authors: K
authors: Sundquist
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors: K
authors: K
authors: Hemminki
mesh_terms: D000328:Adult; D000368:Aged; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D016208:Databases, Factual; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D013548:Sweden
keywords: Concordance; Familial CNS tumor; Family history; First-degree relatives; Histological agreement