A genetically determined dose-volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy

Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1410-6. doi: 10.1016/j.ijrobp.2007.02.052. Epub 2007 May 9.


Purpose: 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 and materials: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Analysis of Variance
  • Ataxia Telangiectasia Mutated Proteins
  • Brachytherapy / adverse effects*
  • Cell Cycle Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Dose-Response Relationship, Radiation
  • Erectile Dysfunction / genetics
  • Gastrointestinal Hemorrhage / genetics*
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Male
  • Middle Aged
  • Mutation, Missense / genetics*
  • Palladium / therapeutic use
  • Proctitis / genetics
  • Prostatic Neoplasms / radiotherapy*
  • Protein Serine-Threonine Kinases / genetics*
  • Radioisotopes / therapeutic use
  • Rectal Diseases / genetics*
  • Rectum / radiation effects
  • Tumor Suppressor Proteins / genetics*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Iodine Radioisotopes
  • Radioisotopes
  • Tumor Suppressor Proteins
  • Palladium
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases