title: Lymphocyte telomere length correlates with in vitro radiosensitivity in breast cancer cases but is not predictive of acute normal tissue reactions to radiotherapy.
abstract: OBJECTIVE
  To examine the hypothesis that lymphocyte telomere length may be predictive of both breast cancer susceptibility and severity of acute reactions to radiotherapy.
  
  
  METHODS
  Peripheral blood lymphocyte cultures from breast cancer patients (with normal or severe skin reactions to radiotherapy) and normal individuals were assessed for in vitro radiosensitivity as measured by apoptosis, cell cycle delay and cytotoxicity. Telomere lengths were determined by a flow cytometric fluorescence in situ hybridization assay (FLOW-FISH).
  
  
  RESULTS
  Female breast cancer cases (n = 24) had reduced lymphocyte telomere lengths by comparison with healthy controls (n = 20, p < 0.04). However, the average age of healthy controls was less (45.4) than cases (53). When the control group was modified to give a better age match (51.5, n = 13) the reduced telomere length in cases was not significantly different from controls. Lymphocytes from breast cancer cases also showed reduced cell cycle delay (p < 0.001) and increased apoptosis (p < 0.01) following irradiation in vitro at 3 and 5 Gy respectively, compared to healthy controls. Statistical significance was maintained with the improved age matching of groups. Comparison of lymphocytes from breast cancer patients with normal (n = 11) and severe (n = 13) skin reactions to radiotherapy failed to identify differences in telomere length or cellular radiosensitivity in this limited sample.
  
  
  CONCLUSIONS
  This study adds to the evidence suggesting a correlation between altered cellular radiosensitivity and breast cancer. However, in the cases investigated, telomere length does not appear to be predictive of acute skin reactions to radiotherapy.
authors.affiliation: Radiation Effects Department, Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Radiation Protection Division, Chilton, Didcot, Oxfordshire, UK.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Naomi
authors.initials: N
authors.lastname: Robertson
authors.forename: Theodora
authors.initials: T
authors.lastname: Tsigani
authors.forename: Paul
authors.initials: P
authors.lastname: Finnon
authors.forename: David
authors.initials: D
authors.lastname: Scott
authors.forename: Ed
authors.initials: E
authors.lastname: Levine
authors.forename: Christophe
authors.initials: C
authors.lastname: Badie
authors.forename: Simon
authors.initials: S
authors.lastname: Bouffler
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000235:genetics* / Q000473:pathology*; D011836:Radiation Tolerance / Q000235:genetics*; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured