title: Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence.
abstract: BACKGROUND
  To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer.
  
  
  METHODS
  We conducted a nested case-control study of men who had a radical prostatectomy in 1993 to 2001. A total of 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single-nucleotide polymorphisms (SNP) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR, IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate OR and 95% confidence intervals (CI).
  
  
  RESULTS
  The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10 (IL-10), was associated with a higher risk of recurrence (OR = 1.76, 95% CI: 1.00-3.10), and the minor allele (G) in rs1800896, known to produce more IL-10, was associated with a lower risk of recurrence (OR = 0.66, 95% CI: 0.48-0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and 2 common NOS2 haplotypes were associated with recurrence.
  
  
  CONCLUSIONS
  Variation in IL10, CRP, GSTP1, IL1B, and NOS2 was associated with prostate cancer recurrence independent of pathologic prognostic factors.
  
  
  CONCLUSIONS
  This study supports that genetic variation in immune response and oxidation influence prostate cancer recurrence risk and suggests genetic variation in these pathways may inform prognosis.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dluzniewski
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Wang
authors.forename: Siqun Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.forename: Helen L
authors.initials: HL
authors.lastname: Fedor
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics; D016022:Case-Control Studies; D014644:Genetic Variation; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; D053583:Interleukin-1beta; D016753:Interleukin-10; D002097:C-Reactive Protein; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi