title: Antioxidant and vitamin E transport genes and risk of high-grade prostate cancer and prostate cancer recurrence.
abstract: BACKGROUND
  Observational studies suggest an inverse association between vitamin E and risk of prostate cancer, particularly aggressive tumors. However, three large randomized controlled trials have reported conflicting results. Thus, we examined circulating vitamin E and vitamin E-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with clinically organ-confined disease.
  
  
  METHODS
  We measured circulating α- and γ-tocopherol and genotyped 30 SNPs in SOD1, SOD2, SOD3, TTPA, and SEC14L2 among 573 men with organ-confined prostate cancer who underwent radical prostatectomy. We examined associations between circulating vitamin E, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥ 8 or 7 with primary score ≥ 4; n = 117) using logistic regression, and risk of recurrence (56 events; 3.7 years median follow-up) using Cox proportional hazards regression.
  
  
  RESULTS
  Circulating γ-tocopherol was associated with an increased risk of high-grade prostate cancer (Q4 v. Q1 odds ratio [OR] = 1.87; 95% confidence intervals [CI]: 0.97-3.58; P trend =0.02). The less common allele in SOD3 rs699473 was associated with an increased risk of high-grade disease (T > C: OR = 1.40, 95% CI: 1.04-1.89). Two independent SNPs in SOD1 were inversely associated with prostate cancer recurrence in additive models (rs17884057 hazard ratio [HR] = 0.49, 95%CI: 0.25-0.96; rs9967983 HR = 0.62, 95% CI: 0.40-0.95).
  
  
  CONCLUSIONS
  Among men with clinically organ-confined prostate cancer, genetic variation in SOD may be associated with risk of high-grade disease at diagnosis and disease recurrence. Circulating γ-tocopherol levels may also be associated with an increased risk of high-grade disease at diagnosis.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Bauer
authors.forename: Erin L
authors.initials: EL
authors.lastname: Richman
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sosa
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D015534:Trans-Activators / Q000235:genetics; D014810:Vitamin E / Q000235:genetics*; D024502:alpha-Tocopherol / Q000097:blood; D024504:gamma-Tocopherol / Q000097:blood*; D000099156:Superoxide Dismutase 2
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008074:Lipoproteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D015534:Trans-Activators; D014810:Vitamin E; D024502:alpha-Tocopherol; D024504:gamma-Tocopherol; D000099156:Superoxide Dismutase 2; C432422:SEC14L2 protein, human; C000606290:SOD1 protein, human; C017763:alpha-tocopherol transfer protein; C441642:SOD3 protein, human
keywords: Gleason grade; genetic polymorphisms; prostate cancer; recurrence; vitamin E
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