Urinary 8-oxoguanine as a predictor of survival in patients undergoing radiotherapy

Cancer Epidemiol Biomarkers Prev. 2012 Apr;21(4):629-34. doi: 10.1158/1055-9965.EPI-11-0981. Epub 2012 Feb 1.

Abstract

Background: Because of the importance to identify prognostic indicator for radiotherapy, herein we decided to check whether the parameters which describe oxidative stress/DNA damage may be used as a marker of the therapy. The aim of this work was to investigate whether fractionated radiotherapy of patients with cancer (n = 99) is responsible for oxidative DNA damage on the level of the whole organism and whether the biomarkers of the damage such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and its modified base 8-oxo-7,8-dihydroguanine (8-oxo-Gua) in urine and DNA may be used as a predictor of radiotherapy success.

Methods: All the aforementioned modifications were analyzed using techniques which involve high-performance liquid chromatography/electrochemical detection (HPLC/EC) or HPLC/gas chromatography-mass spectroscopy (GC-MS).

Results: Of all analyzed parameters only patients with significantly elevated urinary excretion of the 8-oxo-Gua with concomitant unchanged level of 8-oxo-dG in leukocytes DNA in the samples collected 24 hours after the first fraction in comparison to the initial level have significantly increased survival time (60 months after the treatment, survival of 50% of the patients who fulfill the above mentioned criteria, in comparison with 10% of the patients who did not).

Conclusions: Results of our work suggest that patients with higher urinary 8-oxo-Gua and concomitant stable level of 8-oxo-dG in leukocytes DNA, after 24 hours of the first dose should be regarded as better responder to radiotherapy as being at lower risk of mortality.

Impact: The above mentioned statement could make it possible to use these parameters as markers to predict the clinical success.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / urine*
  • Chromatography, High Pressure Liquid
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / urine
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / urine
  • Humans
  • Leukocytes / metabolism
  • Leukocytes / radiation effects
  • Male
  • Middle Aged
  • Neoplasms / mortality*
  • Neoplasms / radiotherapy*
  • Neoplasms / urine
  • Oxidation-Reduction
  • Oxidative Stress
  • Prognosis
  • Radiation Oncology
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • 8-hydroxyguanine
  • Guanine
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine