title: Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: F J
authors.initials: FJ
authors.lastname: Hosking
authors.forename: D
authors.initials: D
authors.lastname: Feldman
authors.forename: R
authors.initials: R
authors.lastname: Bruchim
authors.forename: B
authors.initials: B
authors.lastname: Olver
authors.forename: A
authors.initials: A
authors.lastname: Lloyd
authors.forename: J
authors.initials: J
authors.lastname: Vijayakrishnan
authors.forename: P
authors.initials: P
authors.lastname: Flint-Richter
authors.forename: P
authors.initials: P
authors.lastname: Broderick
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
authors.forename: S
authors.initials: S
authors.lastname: Sadetzki
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005190:Family; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium; D008577:Meningeal Neoplasms / Q000209:etiology / Q000235:genetics*; D008579:Meningioma / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011839:Radiation, Ionizing; D011878:Radiotherapy / Q000009:adverse effects