title: Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer.
abstract: OBJECTIVE
  Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy.
  
  
  METHODS
  Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses.
  
  
  RESULTS
  Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0Gy), irradiated (4Gy) or radiation response (4-0Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished.
  
  
  CONCLUSIONS
  Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.
authors.affiliation: Health Protection Agency, Didcot, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Finnon
authors.forename: Sylwia
authors.initials: S
authors.lastname: Kabacik
authors.forename: Alan
authors.initials: A
authors.lastname: MacKay
authors.forename: Claudine
authors.initials: C
authors.lastname: Raffy
authors.forename: Roger
authors.initials: R
authors.lastname: A'Hern
authors.forename: Roger
authors.initials: R
authors.lastname: Owen
authors.forename: Christophe
authors.initials: C
authors.lastname: Badie
authors.forename: John
authors.initials: J
authors.lastname: Yarnold
authors.forename: Simon
authors.initials: S
authors.lastname: Bouffler
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery; D016022:Case-Control Studies; D016000:Cluster Analysis; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D015162:Micronucleus Tests; D008875:Middle Aged; D011836:Radiation Tolerance / Q000235:genetics*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic