Genetic predictors of adverse radiotherapy effects: the Gene-PARE project

Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):646-55. doi: 10.1016/j.ijrobp.2006.03.006.

Abstract

Purpose: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal.

Methods and materials: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work.

Results: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy.

Conclusions: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.

Publication types

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

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Chromatography, High Pressure Liquid / methods
  • DNA-Binding Proteins / genetics
  • Deoxyribonuclease I / analysis
  • Humans
  • Mutation / genetics
  • Neoplasms / radiotherapy
  • Nuclear Proteins / genetics
  • Phosphoproteins / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Predictive Value of Tests
  • Protein-Serine-Threonine Kinases / genetics
  • Radiation Injuries / genetics*
  • Radiation Tolerance / genetics*
  • Radiotherapy / adverse effects*
  • Superoxide Dismutase / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta1
  • Tumor Suppressor Proteins / genetics
  • X-ray Repair Cross Complementing Protein 1

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • RAD21 protein, human
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Suppressor Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Superoxide Dismutase
  • superoxide dismutase 2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • Deoxyribonuclease I