학술논문

Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping.
Document Type
Journal Article
Source
British Journal of Cancer. 3/15/2011, Vol. 104 Issue 6, p1049-1054. 6p. 2 Charts, 3 Graphs.
Subject
*Brain tumors
*Meningioma
*Ionizing radiation
*Molecular diagnosis
*Genetic polymorphisms
*Radiotherapy
*Tinea capitis
*Comparative studies
*Disease susceptibility
*Families
*Gene mapping
*Genetics
*Research methodology
*Medical cooperation
*Radiation
*Radiation carcinogenesis
*Research
*Meninges
*Evaluation research
*Case-control method
*Secondary primary cancer
*Sequence analysis
*Tumors
Language
ISSN
0007-0920
Abstract
Background: 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.Methods: 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.Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]