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.
| Original language | English |
|---|---|
| Pages (from-to) | 761-766 |
| Number of pages | 6 |
| Journal | Cancer |
| Volume | 109 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 15 2007 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Oncology
Cite this
Brain tumors in individuals with Familial Adenomatous Polyposis : A cancer registry experience and pooled case report analysis. / Attard, Thomas M.; Giglio, Pierre; Koppula, Sireesha; Snyder, Carrie; Lynch, Henry T.
In: Cancer, Vol. 109, No. 4, 15.02.2007, p. 761-766.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Brain tumors in individuals with Familial Adenomatous Polyposis
T2 - A cancer registry experience and pooled case report analysis
AU - Attard, Thomas M.
AU - Giglio, Pierre
AU - Koppula, Sireesha
AU - Snyder, Carrie
AU - Lynch, Henry T.
PY - 2007/2/15
Y1 - 2007/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33846896438&partnerID=8YFLogxK
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U2 - 10.1002/cncr.22475
DO - 10.1002/cncr.22475
M3 - Article
C2 - 17238184
AN - SCOPUS:33846896438
VL - 109
SP - 761
EP - 766
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 4
ER -