Genotyping of Patients with Sporadic and Radiation-Associated Meningiomas
- Siegal Sadetzki1,6,
- Pazit Flint-Richter1,6,
- Sigal Starinsky3,6,
- Ilya Novikov2,
- Yehuda Lerman5,6,
- Boleslaw Goldman4,6 and
- Eitan Friedman3,6
- 1Cancer and Radiation Epidemiology Unit and 2Biostatistics Unit, Gertner Institute and 3Susanne Levy-Gertner Oncogenetics Unit, Sheba Medical Center; 4Danek Gertner Institute of Genetics, Tel Hashomer, Israel; 5Occupational and Environmental National Health Institute, Ra'anana, Israel; and 6Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Requests for reprints:
Siegal Sadetzki, Cancer Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel 52621. Phone: 972-3-5303262; Fax: 972-3-5348360. E-mail: siegals{at}gertner.health.gov.il
Abstract
Ionizing radiation is the most established risk factor for meningioma formation. Our aim was to evaluate the main effect of selected candidate genes on the development of meningioma and their possible interaction with ionizing radiation in the causation of this tumor. The total study population included 440 cases and controls: 150 meningioma patients who were irradiated for tinea capitis in childhood, 129 individuals who were similarly irradiated but did not develop meningioma, 69 meningioma patients with no previous history of irradiation, and 92 asymptomatic population controls. DNA from peripheral blood samples was genotyped for single nucleotide polymorphisms (SNP) in 12 genes: NF2, XRCC1, XRCC3, XRCC5, ERCC2, Ki-ras, p16, cyclin D1, PTEN, E-cadherin, TGFB1, and TGFBR2. SNP analysis was done using the MassArray system (Sequenom, San Diego, CA) and computerized analysis by SpectroTYPER. Logistic regressions were applied to evaluate main effect of each gene on meningioma formation and interaction between gene and radiation. Intragenic SNPs in the Ki-ras and ERCC2 genes were associated with meningioma risk (odds ratio, 1.76; 95% confidence interval, 1.07-2.92 and odds ratio, 1.68; 95% confidence interval, 1.00-2.84, respectively). A significant interaction was found between radiation and cyclin D1 and p16 SNPs (P for interaction = 0.005 and 0.057, respectively). Our findings suggest that Ki-ras and ERCC2 SNPs are possible markers for meningioma formation, whereas cyclin D1 and p16 SNPs may be markers of genes that have an inverse effect on the risk to develop meningioma in irradiated and nonirradiated populations.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted December 13, 2004.
- Received May 17, 2004.
- Revision received November 24, 2004.
