title: A peripheral circulating TH1 cytokine profile is inversely associated with prostate cancer risk in CLUE II.
abstract: BACKGROUND
  TH1 cytokines, such as IFNγ and TNFα, and potentially innate cytokines, such as IL6, can potentiate the immune response to tumor. Cytokines, such as IL1β, IL8, and IL10, may suppress anticancer immunity. Thus, we prospectively evaluated the association between peripheral-cytokine concentrations and prostate cancer.
  
  
  METHODS
  We conducted an age-race matched case-control study (268 pairs) of incident prostate cancer in CLUE-II. We measured plasma IFNγ, IL10, IL12p70, IL1β, IL6, IL8, and TNFα concentrations using an ultrasensitive multiplex kit. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression.
  
  
  RESULTS
  The OR of prostate cancer decreased across quartiles of IFNγ (highest vs. lowest quartiles: OR, 0.49; 95% CI, 0.30-0.81; Ptrend = 0.006), TNFα (OR, 0.56; 95% CI, 0.33-0.96; Ptrend = 0.01), and IL6 (OR, 0.46; 95% CI, 0.26-0.79; Ptrend = 0.007). Higher TNFα (OR, 0.28; 95% CI, 0.09-0.85; Ptrend = 0.01) and IL6 (OR, 0.20; 95% CI, 0.06-0.67; Ptrend = 0.003) concentrations were associated with lower Gleason sum ≥7 disease risk. Other cytokines were not as clearly associated with risk.
  
  
  CONCLUSIONS
  Men with a prediagnostic circulating TH1 profile and higher IL6 may have a lower risk of prostate cancer, including aggressive disease. Whether this profile reflects (i) an intraprostatic immune environment in benign tissue that protects against prostate cancer, (ii) the immune milieu in response to a prostate adenocarcinoma that inhibits tumor growth and detectability, and/or (iii) a systemic immune profile that mediates the influence of modifiable factors on risk, warrants additional study.
  
  
  CONCLUSIONS
  Identifying specific inflammatory cytokines associated with prostate cancer may lead to improved prevention and treatment strategies.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland. Center for Learning Health Care, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Nrupen A
authors.initials: NA
authors.lastname: Bhavsar
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.affiliation: Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. Department of Immunology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Peskoe
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Djeneba
authors.initials: D
authors.lastname: Dabitao
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.affiliation: Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. eplatz@jhsph.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
mesh_terms: D016022:Case-Control Studies; D016207:Cytokines; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha