title: A genetically determined dose-volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy.
abstract: OBJECTIVE
  To examine whether possession of genetic alterations in the ATM (ataxia telangiectasia) gene is associated with rectal bleeding in a dose-dependent and volume-dependent manner.
  
  
  METHODS
  One hundred eight prostate cancer patients who underwent brachytherapy using either an (125)I implant, a (103)Pd implant, or the combination of external beam radiotherapy with a (103)Pd implant and had a minimum of 1 year follow-up were screened for DNA sequence variations in the 62 coding exons of the ATM gene using denaturing high-performance liquid chromatography. Rectal dose was reported as the volume (in cubic centimeters) of rectum receiving the brachytherapy prescription dose. The two-sided Fisher exact test was used to compare differences in proportions.
  
  
  RESULTS
  A significant correlation between the presence of any ATM sequence alteration and Grade 1 to 2 proctitis was obtained when the radiation dose to rectal tissue was quantified. Rectal bleeding occurred in 4 of 13 patients (31%) with a variant versus 1 of 23 (4%) without a genetic alteration for patients who had <0.7 cm(3) of rectal tissue receiving the implant prescription dose (p = 0.05). Of patients in whom 0.7-1.4 cm(3) of the rectum received the implant prescription, 4 of 11 (36%) with an ATM alteration exhibited Grade 1 to 2 proctitis, whereas 1 of 21 (5%) without a variant (p = 0.04) developed this radiation-induced late effect.
  
  
  CONCLUSIONS
  The possession of genetic variants in the ATM gene is associated with the development of radiation-induced proctitis after prostate cancer radiotherapy for patients who receive the full prescription dose to either a low or a moderate volume of rectal tissue.
authors.affiliation: Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA. jamie.cesaretti@msnyu.health.org
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Cesaretti
authors.forename: Richard G
authors.initials: RG
authors.lastname: Stock
authors.forename: David P
authors.initials: DP
authors.lastname: Atencio
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Peters
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Peters
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Burri
authors.forename: Nelson N
authors.initials: NN
authors.lastname: Stone
authors.forename: Barry S
authors.initials: BS
authors.lastname: Rosenstein
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D064007:Ataxia Telangiectasia Mutated Proteins; D001918:Brachytherapy / Q000009:adverse effects*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D007172:Erectile Dysfunction / Q000235:genetics; D006471:Gastrointestinal Hemorrhage / Q000235:genetics*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010165:Palladium / Q000627:therapeutic use; D011349:Proctitis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011868:Radioisotopes / Q000627:therapeutic use; D012002:Rectal Diseases / Q000235:genetics*; D012007:Rectum / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D025521:Tumor Suppressor Proteins; D010165:Palladium; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases