Single-nucleotide polymorphisms studied for associations with urinary toxicity from (125)I prostate brachytherapy implants

Brachytherapy. 2014 May-Jun;13(3):285-91. doi: 10.1016/j.brachy.2014.02.002. Epub 2014 Mar 18.

Abstract

Purpose: To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a (125)I prostate brachytherapy implant.

Methods and materials: Genomic DNA from 296 men treated with (125)I prostate brachytherapy monotherapy was extracted from saliva samples for this study. A retrospective database was compiled including clinical, dosimetric, and toxicity data for this cohort of patients. Fourteen candidate single-nucleotide polymorphism (SNPs) from 13 genes (TP53, ERCC2, GSTP1, NOS, TGFβ1, MSH6, RAD51, ATM, LIG4, XRCC1, XRCC3, GSTA1, and SOD2) were tested in this cohort for correlations with toxicity.

Results: This study identified 217 men with at least 2 years of followup. Of these, 39 patients developed Grade ≥2 late urinary complications with a transurethral resection of prostate, urethral stricture, gross hematuria, or a sustained increase in their International Prostate Symptom Score. The only clinical or dosimetric factor that was associated with late urinary toxicity was age (p = 0.02). None of the 14 SNPs tested in this study were associated with late urinary toxicity in the univariate analysis.

Conclusions: This study identified age as the only variable being associated with late urinary toxicity. However, the small sample size and the candidate gene approach used in this study mean that further investigations are essential. Genome-wide association studies are emerging as the preferred approach for future radiogenomic studies to overcome the limitations from a candidate gene approach.

Keywords: Brachytherapy; Prostate cancer; Single-nucleotide polymorphisms; Urinary toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Aged
  • Alberta
  • Brachytherapy / adverse effects*
  • Brachytherapy / methods
  • DNA-Binding Proteins
  • Genetic Predisposition to Disease
  • Humans
  • Iodine Radioisotopes / adverse effects
  • Iodine Radioisotopes / therapeutic use
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Prostatic Neoplasms / complications
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / radiotherapy*
  • Retrospective Studies
  • Urologic Diseases / etiology*
  • Urologic Diseases / genetics
  • X-ray Repair Cross Complementing Protein 1

Substances

  • DNA-Binding Proteins
  • Iodine Radioisotopes
  • X-ray Repair Cross Complementing Protein 1
  • X-ray repair cross complementing protein 3
  • XRCC1 protein, human