title: Brain tumors in individuals with familial adenomatous polyposis: a cancer registry experience and pooled case report analysis.
abstract: BACKGROUND
  Most individuals with Familial Adenomatous Polyposis (FAP) harbor mutations in the APC gene on chromosome 5q21. They are at an increased risk of brain tumors, including cerebellar medulloblastoma, when compared with the general population (Brain Tumor Polyposis-BTP Type 2). Genotype-phenotype correlations between APC gene mutations and central nervous system (CNS) tumors have, thus far not been successful. Herein the authors have pooled their registry experience in BTP type 2 with the published reports.
  
  
  METHODS
  The authors analyzed their established hereditary CRC Registry for brain tumors in FAP pedigrees (56 families, 213 individuals), pooled their patients with BTP and known APC mutations with those reported thus far elsewhere, and compared the resulting mutation distribution of FAP-BTP with the mutation distribution for APC mutations in the US.
  
  
  RESULTS
  Twenty-eight patients from 24 families were accrued, the most common brain tumor in BTP was medulloblastoma (60%) predominantly in females (12:5) under the age of 20 (mean age 14.7 SD 9.2). Other histologic subtypes included astrocytoma and ependymoma. Analysis of the pooled APC mutation data by Chi-square test of association shows an odds ratio of 3.7 (P < .005) for all brain tumor subtypes and 13.1 (P < .001) for medulloblastoma in patients harboring segment 2 APC mutation (codons 679-1224) compared to nonsegment 2 mutation.
  
  
  CONCLUSIONS
  In patients with FAP and identifiable APC gene mutation, CNS tumors, especially medulloblastoma which developed in most cases during childhood, are more common in females with FAP and APC gene mutation in codons 686-1217. Further studies are necessary to determine if this observation and the natural history of medulloblastoma in children justifies novel, aggressive, targeted screening of at-risk individuals.
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, Creighton University School of Medicine, Omaha, Nebraska 68198, USA. tattard@unmc.edu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Attard
authors.forename: Pierre
authors.initials: P
authors.lastname: Giglio
authors.forename: Sireesha
authors.initials: S
authors.lastname: Koppula
authors.forename: Carrie
authors.initials: C
authors.lastname: Snyder
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000150:complications* / Q000235:genetics; D002648:Child; D003062:Codon; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012042:Registries
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003062:Codon