Genotyping of Patients with Sporadic and Radiation-Associated Meningiomas

Tel Aviv University, Tell Afif, Tel Aviv, Israel
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 05/2005; 14(4):969-76. DOI: 10.1158/1055-9965.EPI-04-0366
Source: PubMed


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.

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    • "The prevalence of meningioma was reported to be 6/100,000 individuals annually in the United States (3). Environmental factors, such as ionizing radiation (4–7), hormones (8–12), head trauma (13,14) and cell phone use (15,16), as well as genetic factors, contribute to the pathogenesis of meningioma (17–19). "
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    ABSTRACT: Several epidemiological studies suggested that methionine synthase (MTRR) rs1801394 and methionine synthase reductase (MTR) rs1805087 polymorphisms may be involved in the risk of meningioma in adults; however, the results from different case-control studies have been inconsistent. Therefore, we performed a meta-analysis to investigate the association of MTRR and MTR polymorphisms with meningioma. PubMed, Web of Knowledge, China National Knowledge Infrastructure and Wanfang databases were searched up to October 30, 2013 and 3 publications, involving 7 case-control studies, were finally included. Following data extraction, a meta-analysis was conducted using Stata 12.0 software. The pooled results based on the fixed effects model demonstrated that the MTRR rs1801394 polymorphism was associated with an increased risk of meningioma [odds ratio (OR)=1.18, 95% confidence interval (CI): 1.05-1.32 for G vs. A; OR=1.41, 95% CI: 1.12-1.77 for GG vs. AA; OR=1.08, 95% CI: 0.94-1.33 for AG vs. AA; OR=1.19, 95% CI: 1.01-1.40 for (AG+GG) vs. AA; and OR=1.32, 95% CI: 1.07-1.63 for GG vs. (AG+AA)]; however, an association between the MTR rs1805087 polymorphism and the risk of meningioma was not identified [OR=0.99, 95% CI: 0.88-1.12 for G vs. A; OR=1.09, 95% CI: 0.80-1.48 for GG vs. AA; OR=0.95, 95% CI: 0.82-1.11 for AG vs. AA; OR=0.97, 95% CI: 0.84-1.13 for (AG+GG) vs. AA; and OR=1.09, 95% CI: 0.80-1.48 for GG vs. (AG+AA)]. Therefore, the currently available evidence suggests that the MTRR rs1801394 polymorphism may increase the risk of meningioma, whereas the MTRR rs1801394 polymorphism is not associated with meningioma.
    Full-text · Article · May 2014
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    • "Sadetzki et al. reported that the genotype of KRAS was related to the increased the risk of (nearly 2 fold) meningioma [47]. VDR expression rates were associated with KRAS mutation in several cancer types. "
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    ABSTRACT: Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR) gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases) and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP). Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9%) compared with controls (2.5%), and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.
    Full-text · Article · Apr 2013
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    • "The age at diagnosis for the RAM patients ranged from 35 to 69 years (mean 48.7±9.2). Validation for irradiation status and for tumour pathology was performed for all of these family members, using medical records for pathology verification and a set of criteria that were used in previous studies (Sadetzki et al, 2005b) for irradiation verification. "
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    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.
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