Journal
BRITISH JOURNAL OF CANCER
Volume 104, Issue 6, Pages 1049-1054Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2011.61
Keywords
ionising radiation; meningioma; genetic; sensitivity
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Funding
- Cancer Research UK [C1298/A8780, C1298/A8362]
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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 x 10(-5)), 18q21.31 (P = 2.8 x 10(-5)) and 10q21.3 (P = 1.6 x 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. British Journal of Cancer (2011) 104, 1049-1054. doi: 10.1038/bjc.2011.61 www.bjcancer.com
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