title: Single-nucleotide polymorphisms studied for associations with urinary toxicity from (125)I prostate brachytherapy implants.
abstract: OBJECTIVE
  To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a (125)I prostate brachytherapy implant.
  
  
  METHODS
  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.
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: Nawaid.Usmani@albertahealthservices.ca.
authors.forename: Nawaid
authors.initials: N
authors.lastname: Usmani
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Nelson
authors.initials: N
authors.lastname: Leong
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Martell
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Lanna
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; Division of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Pervez
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Pedersen
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Don
authors.initials: D
authors.lastname: Yee
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Murtha
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Amanie
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; Division of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Sloboda
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; Division of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Murray
authors.affiliation: Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Parliament
mesh_terms: D017677:Age Distribution; D000368:Aged; D000416:Alberta; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D004268:DNA-Binding Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000150:complications / Q000235:genetics / Q000532:radiotherapy*; D012189:Retrospective Studies; D014570:Urologic Diseases / Q000209:etiology* / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D007457:Iodine Radioisotopes; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human
keywords: Brachytherapy; Prostate cancer; Single-nucleotide polymorphisms; Urinary toxicity