title: Key genes involved in the immune response are generally not associated with intraprostatic inflammation in men without a prostate cancer diagnosis: Results from the prostate cancer prevention trial.
abstract: BACKGROUND
  We previously reported that both intraprostatic inflammation and SNPs in genes involved in the immune response are associated with prostate cancer risk and disease grade. In the present study, we evaluated the association between these SNPs and intraprostatic inflammation in men without a prostate cancer diagnosis.
  
  
  METHODS
  Included in this cross-sectional study were 205 white controls from a case-control study nested in the placebo arm of the Prostate Cancer Prevention Trial. We analyzed inflammation data from the review of H&E-stained prostate tissue sections from biopsies performed per protocol at the end of the trial irrespective of clinical indication, and data for 16 SNPs in key genes involved in the immune response (IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, TNFA; 7 tagSNPs in IL10). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between carrying at least one minor allele and having at least one biopsy core (of a mean of three reviewed) with inflammation.
  
  
  RESULTS
  None of the SNPs evaluated was statistically significantly associated with having at least one core with inflammation. However, possible inverse associations were present for carrying the minor allele of rs2069762 (G) in IL2 (OR = 0.51, 95%CI 0.25-1.02); carrying two copies of the minor allele of rs1800871 (T) of IL10 (OR = 0.29, 95%CI 0.08-1.00); and carrying the minor allele of rs486907 (A) in RNASEL (OR = 0.52, 95%CI 0.26-1.06). After creating a genetic risk score from the three SNPs possibly associated with inflammation, the odds of inflammation increased with increasing number of risk alleles (P-trend = 0.008).
  
  
  CONCLUSIONS
  While our findings do not generally support a cross-sectional link between individual SNPs in key genes involved in the immune response and intraprostatic inflammation in men without a prostate cancer diagnosis, they do suggest that some of these variants when in combination may be associated with intraprostatic inflammation in benign tissue.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Danyelle A
authors.initials: DA
authors.lastname: Winchester
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Department of Pathology, Kocaeli University School of Medicine, Kocaeli, Turkey.
authors.forename: Bora
authors.initials: B
authors.lastname: Gurel
authors.affiliation: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Cathee
authors.initials: C
authors.lastname: Till
authors.affiliation: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Goodman
authors.affiliation: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Johnson-Pais
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leach
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.affiliation: Program for Personalized Cancer Care and Department of Surgery, NorthShore University Health System, Evanston, Illinois.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Program for Personalized Cancer Care and Department of Surgery, NorthShore University Health System, Evanston, Illinois.|Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
authors.affiliation: Moores Cancer Center, University of California San Diego, La Jolla, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Parnes
authors.affiliation: James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University 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: James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.|Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University 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 Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.|James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004722:Endoribonucleases / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000276:immunology / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
chemical_list: D007376:Interleukin-2; D016753:Interleukin-10; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
keywords: genes; inflammation; prostate cancer