FaCD Online Syndrome Fact Sheet

Last updated: 23 Jul 2009

Name: Brain Tumors, Familial Clustering of

Synonym: incl. Familial Glioma

Mode of Inheritance: multifact?/ AR?/ AD ?

OMIM number: 137800  

Tumor features

brain, sarcoma of the
choroid plexus papilloma
Ewing sarcoma
glioblastoma (multiforme)
glioma of the brain
prostate cancer

Tumor features (possible)

breast cancer
colon cancer
gastric cancer
Hodgkin disease (Hodgkin's lymphoma)
melanoma, cutaneous


Familial occurrence of brain tumors has predominantly been reported in sibs, however in some cases the tumors have been found in successive generations[1-5,33]. The most frequent tumors in these clusters are astrocytoma, medulloblastoma[6,7] and glioblastoma[8]. Less frequently, choroid plexus papillomas[9,35], ependymomas[10] and sarcomas[11] have been reported.

Figures on the percentage of brain tumors being familial are rare. In general, family history of cancer in children with brain tumors is unremarkable[32]. Estimates for astrocytomas range from less than 1 % to 14 % [12]. In the Swedish Family-Cancer Database, which included 2060 childhood brain tumors, 1.3% of brain tumor patients had a parent with nervous system cancer Some studies conclude that a family history of brain tumors or cancer in general do not significantly contribute to glioma risk in adults and brain tumor risk in children[13-17]. Others found that the occurrence of childhood brain tumor is associated with an increased risk of developing central-nervous-system tumors, leukemia and childhood tumors in relatives[18-20]. One study found a particularly strong association between parental meningioma and brain astrocytoma in the offspring[20]. Malmer et al.[26] studied cancer risk in the first-degree relatives of Swedish astrocytoma patients and found an increased risk for astrocytomas (relative risk 2.1) but not for other primary brain tumors in these relatives. In general, there appears to be no strong relationship between childhood brain tumors occurrence and cancer (any type) in relatives[32,34].

Hill et al reported that in individuals with a family history of a brain cancer or a brain tumor, risk of glioma was 1.6 and 3.0, respectively, in comparison with those without such family histories. Increased risks were also reported for a family history of stomach (OR 2.2), colon (OR 1.4), or prostate cancer (OR 2.1) or Hodgkin disease (OR 2.4)[21]. In another paper they reported that risk of meningioma was increased among those with a family history of a benign brain tumor (OR 4.5) or melanoma (OR 4.2). A family history of breast cancer was associated with an elevated meningioma risk among participants aged 18 to 49 years (OR 3.9) but a reduced risk among older individuals[22].

In general, the familial clustering of gliomas may be associated with a range of congenital malformations and is a genetically heterogeneous group[2]. Relatives of patients with Ewing sarcoma or prostate cancer are at increased risk to develop brain tumors[24;25]. Significantly more colon cancer was observed in first-degree relatives of children with brain tumors, although absolute numbers were small[26]. Interestingly, another study reported a significant decrease in colon (and breast) cancer risk for first-degree relatives of astrocytoma patients[23]. Certain variants of enzymes involved in (pro)carcinogen metabolism have been found to be associated with an increased risk of astrocytomas and meningiomas , e.g. GSTT1, GSTM1 and CYP2D6 [27]. A small fraction of familial clustering of gliomas may be contributed to germline TP53 mutations[28-31].


Gliogene 24 04 2013


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