Brain tumors in individuals with familial adenomatous polyposis

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. Cancer 2007 © 2007 American Cancer Society.

Medulloblastoma

“…The APC protein forms part of a “destruction complex” that serves to degrade β-catenin and its loss results in the accumulation of β-catenin in the cytoplasm and nucleus. This specific disruption in the Wnt signaling pathway leads to an increased risk of medulloblastoma in FAP patients as compared to the general population [44, 45]. …”

Expectations for Function and Independence by Childhood Brain Tumors Survivors and Their Mothers

“…Susan, Scott’s mother, has familial adenomatous polyposis (FAP), as do all of Susan’s children, including Scott. FAP results in numerous polyp formations in the colon and a potential increased risk for brain tumors (Attard, Giglio, Koppula, Snyder, & Lynch, 2007), although the family and their clinicians were not aware of the predisposition until after the PNET diagnosis. In this family’s case, FAP ultimately requires total colectomy to avoid colon cancer.…”

Molecular Biology and Genetics of Medulloblastoma

“…APC gene mutations were also identifi ed in 10 of 12 families with FAP in which at least one patient developed a central nervous system tumor, mainly MB (79 %), as an extracolonic manifestation of FAP [ 45 ]. In a recent study on 28 BTP subjects, MB was the most common brain tumor, with young females under the age of 20 most frequently affected [ 46 ]. APC exerts its tumor suppression function by inhibiting the activation of the Wnt signaling pathway preventing the uncontrolled growth of cells and, in turn, the tumorigenic process.…”