title: GermLine Variation in Superoxide Dismutase-2 (SOD2) and Survival Outcomes After Radiation Therapy for Prostate Cancer: Results of a Test and Validation Set Analysis.
abstract: BACKGROUND
  Genetic variants in antioxidant pathways might decrease the efficacy of radiation therapy (RT) by suppressing the generation of reactive oxygen species. We studied the association between single nucleotide polymorphisms (SNPs) in the antioxidant gene superoxide dismutase-2 (SOD2) and cancer-specific outcomes after RT.
  
  
  METHODS
  Among 816 prostate cancer patients who received radiation as primary therapy from the Physicians' Health Study and the Health Professionals Follow-up Study, we evaluated the association of 7 tagging SNPs in SOD2 with lethal prostate cancer (death from prostate cancer or distant metastasis among living patients). We sought to validate findings in a separate cohort of 612 prostate cancer patients treated with RT with a greater proportion of intermediate and high-risk Gleason scores at the Dana-Farber Cancer Institute. Genetic effects were analyzed using a codominant model, using the genotype homozygous for the major allele as baseline.
  
  
  RESULTS
  Among patients who underwent RT in the test cohort, there was a significant association between 3 of the 7 SOD2 SNPs and lethal prostate cancer: rs6917589 (overall P = .006), rs2758331 (P = .04) and the functional valine to alanine polymorphism in rs4880 (P = .04). These SNPs were not associated with outcome among men who had undergone prostatectomy. The associations were not replicated in the validation cohort.
  
  
  CONCLUSIONS
  Germline genetic variation in the SOD2 gene might be a predictive biomarker of response to RT for prostate cancer but is not consistently associated with outcome after RT across prostate cancer cohorts with different clinical characteristics.
authors: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA. Electronic address: dmargalit@lroc.harvard.edu.
authors: Danielle N
authors: DN
authors: Margalit
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors: Kristina M
authors: KM
authors: Jordahl
authors: Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors: Lillian
authors: L
authors: Werner
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors: Xiaodong
authors: X
authors: Wang
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors: Mary
authors: M
authors: Gwo-Shu Lee
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Kathryn L
authors: KL
authors: Penney
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Julie L
authors: JL
authors: Batista
authors: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA.
authors: Neil E
authors: NE
authors: Martin
authors: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.
authors: June M
authors: JM
authors: Chan
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors: Philip W
authors: PW
authors: Kantoff
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Meir J
authors: MJ
authors: Stampfer
authors: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA.
authors: Paul L
authors: PL
authors: Nguyen
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Lorelei A
authors: LA
authors: Mucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D013482:Superoxide Dismutase / Q000235:genetics*; D016896:Treatment Outcome; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: Antioxidant; Free radicals; Predictive biomarkers; Reactive oxygen species; SOD2