Flint-Richter P, Sadetzki SGenetic predisposition for the development of radiation-associated meningioma: an epidemiological study. Lancet Oncol 8(5): 403-410

Tel Aviv University, Tell Afif, Tel Aviv, Israel
The Lancet Oncology (Impact Factor: 24.69). 06/2007; 8(5):403-10. DOI: 10.1016/S1470-2045(07)70107-9
Source: PubMed


Ionising radiation is an established risk factor for meningioma, yet less than 1% of irradiated individuals develop this tumour. Familial aggregation of meningioma is rare. We aimed to assess whether genetic factors can modify the risk for meningioma formation after the initiating effect of radiation, by comparison of the frequency of meningiomas in families that included irradiated and unirradiated siblings.
This study was based on a larger epidemiological, genetic case-control study, and included 525 families that were divided according to irradiation and disease status of each of the family's index participant: 160 had radiation-associated meningioma (RAM); 145 were irradiated and did not develop meningioma; 85 had meningioma with no previous history of irradiation; and 135 were unirradiated and did not develop meningioma. Data were collected by questionnaires.
We found additional first-degree relatives with meningioma in 17 families (11%) in the RAM group, whereas only between one and two such families (1%) were found in the other groups (p<0.0001). All meningiomas seen in the families of the RAM group were in irradiated participants. Also, 22 families (10%) in the RAM group had members with cancers in irradiated sites (including head, neck, and chest) compared with 9 (5%) of irradiated controls (p=0.04).
This dataset of families, which included irradiated and unirradiated, and also affected and unaffected family members, created a natural experiment. Our results support the idea that genetic susceptibility increases the risk of developing meningioma after exposure to radiation. Further studies are needed to identify the specific genes involved in this familial sensitivity to ionising radiation. DNA repair and cell-cycle control genes, such as the ataxia-telangiectasia gene, could be plausible candidates for investigation.

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    • "These studies have demonstrated an over-representation of radiation-associated meningioma (RAM) and other radiation-associated cancers in specific families. This finding indicates that the occurrence of the tumour following the exposure is not a random event, and provides support for the hypothesis of inherited genetic susceptibility to radiation-induced cancers (Flint-Richter and Sadetzki, 2007). "
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