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.
"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). "
[Show abstract][Hide abstract] ABSTRACT: Exposure to ionising radiation is a well-established risk factor for multiple types of tumours, including malignant brain tumours. In the 1950s, radiotherapy was used to treat Tinea Capitis (TC) in thousands of children, mostly of North-African and Middle Eastern origin, during the mass migration to Israel. The over-representation of radiation-associated meningioma (RAM) and other cancers in specific families provide support for inherited genetic susceptibility to radiation-induced cancer.
To test this hypothesis, we genotyped 15 families segregating RAM using high-density single-nucleotide polymorphism (SNP) arrays. Using the family-based association test (FBAT) programme, we tested each polymorphism and haplotype for an association with RAM.
The strongest haplotype associations were attained at 18q21.1 (P=7.5 × 10(-5)), 18q21.31 (P=2.8 × 10(-5)) and 10q21.3 (P=1.6 × 10(-4)). Although associations were not formally statistically significant after adjustment for multiple testing, the 18q21.1 and 10q21.3 associations provide support for a variation in PIAS2, KATNAL2, TCEB3C, TCEB3CL and CTNNA3 genes as risk factors for RAM.
These findings suggest that any underlying genetic susceptibility to RAM is likely to be mediated through the co-inheritance of multiple risk alleles rather than a single major gene locus determining radiosensitivity.
British Journal of Cancer 03/2011; 104(6):1049-54. DOI:10.1038/bjc.2011.61 · 4.84 Impact Factor
"It is not only the difference in cure rates which differentiates between children and adults with regard to cancer radiotherapy, but it is also the enhanced radio-sensitivity of children for most cancer types . The reason for this age effect might be related to the increased susceptibility of the underlying tissue to the mutagenetic effects of therapy at younger age or the higher rate of cell proliferation during the early stages of development  . The scattered radiation in radiotherapy from the treatment volume might be more significant for children than for adults since the body and thus the distance between treatment volume and organ at risk is smaller in a pediatric patient than in an adult. "
[Show abstract][Hide abstract] ABSTRACT: The scattered radiation from the treatment volume might be more significant for children than for adults and, as a consequence, modern radiotherapy treatment techniques such as IMRT and passive proton therapy could potentially increase the number of secondary cancers. In this report, secondary cancer risk resulting from new treatment technologies was estimated for an adult prostate patient and a child.
The organ equivalent dose (OED) concept with a linear-exponential, a plateau and a linear dose-response curve was applied to dose distributions of an adult prostate patient and a child with a rhabdomyosarcoma of the prostate. Conformal radiotherapy, IMRT with 6MV photons and proton therapy were planned. OED (cancer risk) was estimated for the whole body, the rectum and the bladder. In addition, relative cumulative risk was calculated.
Secondary cancer risk in the adult is not more than 15% it increased when IMRT or passive proton therapy was compared to conventional treatment planning. In the child, risk remains practically constant or was even reduced for proton therapy. The cumulative risk in the child relative to that in the adult can be as large as 10-15.
By a comparison between an adult patient and a child treated for a disease of the prostate, it was shown that modern radiotherapy techniques such as IMRT and proton therapy (active and passive) do not increase the risk for secondary cancers.
Radiotherapy and Oncology 09/2008; 89(2):135-40. DOI:10.1016/j.radonc.2008.07.017 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The usual methods for speech signal analysis give a spectrum evaluation on a time interval (20 to 40 ms) larger than the largest pitch period, which eliminates most phonetically relevant information. Our approach consists in a decomposition of the signal into a string of "impulses" defined in the frequency-time domain. The work described in the present paper is done using a filterbank followed by short-time integrators. An "Impulse Coherence Function" is defined ; its maxima are used to mark the places where the impulse are. Classification experiments are carried out, in order to segment the speech wave according to the regularity and similarity of the successive impulses. Applications may be envisioned in the fields of voicing and pitch detection, consonant features recognition, and auditory modeling.
Acoustics, Speech, and Signal Processing, IEEE International Conference on ICASSP '82.; 06/1982
Wieteke M Heidema, Ralph R Scholten, Fred K Lotgering, Marc E A Spaanderman
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