title: Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.
abstract: BACKGROUND
  The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.
  
  
  METHODS
  Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test P < 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts.
  
  
  RESULTS
  Forty-seven markers had positive association values; including one in the SEMA3A promoter region (P = 1.24 x 10(-5)). SEMA3A knockdown enhanced radiation resistance.
  
  
  CONCLUSIONS
  This study identified 47 putative radiosensitivity markers, and suggested a role for SEMA3A in radiosensitivity.
authors.affiliation: RadGenomics Project, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Michikawa
authors.forename: Tomo
authors.initials: T
authors.lastname: Suga
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Mayumi
authors.initials: M
authors.lastname: Iwakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
mesh_terms: D005347:Fibroblasts; D006801:Humans; D018895:Microsatellite Repeats; D009369:Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics*