title: Circulating Antioxidant Levels and Risk of Prostate Cancer by TMPRSS2:ERG.
abstract: BACKGROUND
  Few studies have considered etiological differences across molecular subtypes of prostate cancer, despite potential to improve opportunities for precision prevention of a disease for which modifiable risk factors have remained elusive. Factors that lead to DNA double-strand breaks, such as oxidative stress, may promote the formation of the TMPRSS2:ERG gene fusion in prostate cancer. We tested the hypothesis that increasing levels of pre-diagnostic circulating antioxidants, which may reduce oxidative stress, are associated with lower risk of developing TMPRSS2:ERG positive prostate cancer.
  
  
  METHODS
  We conducted a nested case-control study, including 370 cases and 2,470 controls, to evaluate associations between pre-diagnostic α- and β-carotene, α- and γ-tocopherol, β-cryptoxanthin, lutein, lycopene, retinol, and selenium with the risk of prostate cancer by ERG protein expression status (a marker of TMPRSS2:ERG). Multivariable unconditional polytomous logistic regression was used to calculate odds ratios and 95% confidence intervals.
  
  
  RESULTS
  We did not find any of the antioxidants to be significantly associated with the risk of prostate cancer according to ERG status.
  
  
  CONCLUSIONS
  The results do not support the hypothesis that circulating pre-diagnostic antioxidant levels protect against developing TMPRSS2:ERG positive prostate cancer. Additional studies are needed to explore mechanisms for the development of TMPRSS2:ERG positive disease. Prostate 77: 647-653, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Graff
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California.
authors.forename: Gregory
authors.initials: G
authors.lastname: Judson
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Ahearn
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pettersson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D000071230:Transcriptional Regulator ERG / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000975:Antioxidants; D014408:Biomarkers, Tumor; C072312:ERG protein, human; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
keywords: biomarkers; epidemiology; molecular subtypes